Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5

Mycobacterium tuberculosis can proficiently enter macrophages and diminish complement activation on its cell surface. Within macrophages, the mycobacterium can suppress macrophage apoptosis and survive within the intracellular environment. Previously, we have shown that complement regulatory protein...
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Autor*in:	Maha Ahmed Al-Mozaini [verfasserIn] Anthony G. Tsolaki [verfasserIn] Munirah Abdul-Aziz [verfasserIn] Suhair M. Abozaid [verfasserIn] Mohammed N. Al-Ahdal [verfasserIn] Ansar A. Pathan [verfasserIn] Valarmathy Murugaiah [verfasserIn] Evgeny M. Makarov [verfasserIn] Anuvinder Kaur [verfasserIn] Robert B. Sim [verfasserIn] Uday Kishore [verfasserIn] Lubna Kouser [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	complement cytokine properdin macrophage Mycobacterium tuberculosis Mycobacterium bovis BCG

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 9(2018)
Übergeordnetes Werk:	volume:9 ; year:2018

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2018.00533

Katalog-ID:	DOAJ028478444

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520			\|a Mycobacterium tuberculosis can proficiently enter macrophages and diminish complement activation on its cell surface. Within macrophages, the mycobacterium can suppress macrophage apoptosis and survive within the intracellular environment. Previously, we have shown that complement regulatory proteins such as factor H may interfere with pathogen–macrophage interactions during tuberculosis infection. In this study, we show that Mycobacterium bovis BCG binds properdin, an upregulator of the complement alternative pathway. TSR4+5, a recombinant form of thrombospondin repeats 4 and 5 of human properdin expressed in tandem, which is an inhibitor of the alternative pathway, was also able to bind to M. bovis BCG. Properdin and TSR4+5 were found to inhibit uptake of M. bovis BCG by THP-1 macrophage cells in a dose-dependent manner. Quantitative real-time PCR revealed elevated pro-inflammatory responses (TNF-α, IL-1β, and IL-6) in the presence of properdin or TSR4+5, which gradually decreased over 6 h. Correspondingly, anti-inflammatory responses (IL-10 and TGF-β) showed suppressed levels of expression in the presence of properdin, which gradually increased over 6 h. Multiplex cytokine array analysis also revealed that properdin and TSR4+5 significantly enhanced the pro-inflammatory response (TNF-α, IL-1β, and IL-1α) at 24 h, which declined at 48 h, whereas the anti-inflammatory response (IL-10) was suppressed. Our results suggest that properdin may interfere with mycobacterial entry into macrophages via TSR4 and TSR5, particularly during the initial stages of infection, thus affecting the extracellular survival of the pathogen. This study offers novel insights into the non-complement related functions of properdin during host–pathogen interactions in tuberculosis.
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Indexfelder

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allfields	10.3389/fimmu.2018.00533 doi (DE-627)DOAJ028478444 (DE-599)DOAJ36f7c38f819b4a6fbc5908bb3d060aa6 DE-627 ger DE-627 rakwb eng RC581-607 Maha Ahmed Al-Mozaini verfasserin aut Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mycobacterium tuberculosis can proficiently enter macrophages and diminish complement activation on its cell surface. Within macrophages, the mycobacterium can suppress macrophage apoptosis and survive within the intracellular environment. Previously, we have shown that complement regulatory proteins such as factor H may interfere with pathogen–macrophage interactions during tuberculosis infection. In this study, we show that Mycobacterium bovis BCG binds properdin, an upregulator of the complement alternative pathway. TSR4+5, a recombinant form of thrombospondin repeats 4 and 5 of human properdin expressed in tandem, which is an inhibitor of the alternative pathway, was also able to bind to M. bovis BCG. Properdin and TSR4+5 were found to inhibit uptake of M. bovis BCG by THP-1 macrophage cells in a dose-dependent manner. Quantitative real-time PCR revealed elevated pro-inflammatory responses (TNF-α, IL-1β, and IL-6) in the presence of properdin or TSR4+5, which gradually decreased over 6 h. Correspondingly, anti-inflammatory responses (IL-10 and TGF-β) showed suppressed levels of expression in the presence of properdin, which gradually increased over 6 h. Multiplex cytokine array analysis also revealed that properdin and TSR4+5 significantly enhanced the pro-inflammatory response (TNF-α, IL-1β, and IL-1α) at 24 h, which declined at 48 h, whereas the anti-inflammatory response (IL-10) was suppressed. Our results suggest that properdin may interfere with mycobacterial entry into macrophages via TSR4 and TSR5, particularly during the initial stages of infection, thus affecting the extracellular survival of the pathogen. This study offers novel insights into the non-complement related functions of properdin during host–pathogen interactions in tuberculosis. complement cytokine properdin macrophage Mycobacterium tuberculosis Mycobacterium bovis BCG Immunologic diseases. Allergy Maha Ahmed Al-Mozaini verfasserin aut Anthony G. Tsolaki verfasserin aut Munirah Abdul-Aziz verfasserin aut Munirah Abdul-Aziz verfasserin aut Suhair M. Abozaid verfasserin aut Suhair M. Abozaid verfasserin aut Mohammed N. Al-Ahdal verfasserin aut Ansar A. Pathan verfasserin aut Valarmathy Murugaiah verfasserin aut Evgeny M. Makarov verfasserin aut Anuvinder Kaur verfasserin aut Robert B. Sim verfasserin aut Uday Kishore verfasserin aut Lubna Kouser verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 9(2018) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:9 year:2018 https://doi.org/10.3389/fimmu.2018.00533 kostenfrei https://doaj.org/article/36f7c38f819b4a6fbc5908bb3d060aa6 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2018.00533/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
spelling	10.3389/fimmu.2018.00533 doi (DE-627)DOAJ028478444 (DE-599)DOAJ36f7c38f819b4a6fbc5908bb3d060aa6 DE-627 ger DE-627 rakwb eng RC581-607 Maha Ahmed Al-Mozaini verfasserin aut Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mycobacterium tuberculosis can proficiently enter macrophages and diminish complement activation on its cell surface. Within macrophages, the mycobacterium can suppress macrophage apoptosis and survive within the intracellular environment. Previously, we have shown that complement regulatory proteins such as factor H may interfere with pathogen–macrophage interactions during tuberculosis infection. In this study, we show that Mycobacterium bovis BCG binds properdin, an upregulator of the complement alternative pathway. TSR4+5, a recombinant form of thrombospondin repeats 4 and 5 of human properdin expressed in tandem, which is an inhibitor of the alternative pathway, was also able to bind to M. bovis BCG. Properdin and TSR4+5 were found to inhibit uptake of M. bovis BCG by THP-1 macrophage cells in a dose-dependent manner. Quantitative real-time PCR revealed elevated pro-inflammatory responses (TNF-α, IL-1β, and IL-6) in the presence of properdin or TSR4+5, which gradually decreased over 6 h. Correspondingly, anti-inflammatory responses (IL-10 and TGF-β) showed suppressed levels of expression in the presence of properdin, which gradually increased over 6 h. Multiplex cytokine array analysis also revealed that properdin and TSR4+5 significantly enhanced the pro-inflammatory response (TNF-α, IL-1β, and IL-1α) at 24 h, which declined at 48 h, whereas the anti-inflammatory response (IL-10) was suppressed. Our results suggest that properdin may interfere with mycobacterial entry into macrophages via TSR4 and TSR5, particularly during the initial stages of infection, thus affecting the extracellular survival of the pathogen. This study offers novel insights into the non-complement related functions of properdin during host–pathogen interactions in tuberculosis. complement cytokine properdin macrophage Mycobacterium tuberculosis Mycobacterium bovis BCG Immunologic diseases. Allergy Maha Ahmed Al-Mozaini verfasserin aut Anthony G. Tsolaki verfasserin aut Munirah Abdul-Aziz verfasserin aut Munirah Abdul-Aziz verfasserin aut Suhair M. Abozaid verfasserin aut Suhair M. Abozaid verfasserin aut Mohammed N. Al-Ahdal verfasserin aut Ansar A. Pathan verfasserin aut Valarmathy Murugaiah verfasserin aut Evgeny M. Makarov verfasserin aut Anuvinder Kaur verfasserin aut Robert B. Sim verfasserin aut Uday Kishore verfasserin aut Lubna Kouser verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 9(2018) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:9 year:2018 https://doi.org/10.3389/fimmu.2018.00533 kostenfrei https://doaj.org/article/36f7c38f819b4a6fbc5908bb3d060aa6 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2018.00533/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
allfields_unstemmed	10.3389/fimmu.2018.00533 doi (DE-627)DOAJ028478444 (DE-599)DOAJ36f7c38f819b4a6fbc5908bb3d060aa6 DE-627 ger DE-627 rakwb eng RC581-607 Maha Ahmed Al-Mozaini verfasserin aut Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mycobacterium tuberculosis can proficiently enter macrophages and diminish complement activation on its cell surface. Within macrophages, the mycobacterium can suppress macrophage apoptosis and survive within the intracellular environment. Previously, we have shown that complement regulatory proteins such as factor H may interfere with pathogen–macrophage interactions during tuberculosis infection. In this study, we show that Mycobacterium bovis BCG binds properdin, an upregulator of the complement alternative pathway. TSR4+5, a recombinant form of thrombospondin repeats 4 and 5 of human properdin expressed in tandem, which is an inhibitor of the alternative pathway, was also able to bind to M. bovis BCG. Properdin and TSR4+5 were found to inhibit uptake of M. bovis BCG by THP-1 macrophage cells in a dose-dependent manner. Quantitative real-time PCR revealed elevated pro-inflammatory responses (TNF-α, IL-1β, and IL-6) in the presence of properdin or TSR4+5, which gradually decreased over 6 h. Correspondingly, anti-inflammatory responses (IL-10 and TGF-β) showed suppressed levels of expression in the presence of properdin, which gradually increased over 6 h. Multiplex cytokine array analysis also revealed that properdin and TSR4+5 significantly enhanced the pro-inflammatory response (TNF-α, IL-1β, and IL-1α) at 24 h, which declined at 48 h, whereas the anti-inflammatory response (IL-10) was suppressed. Our results suggest that properdin may interfere with mycobacterial entry into macrophages via TSR4 and TSR5, particularly during the initial stages of infection, thus affecting the extracellular survival of the pathogen. This study offers novel insights into the non-complement related functions of properdin during host–pathogen interactions in tuberculosis. complement cytokine properdin macrophage Mycobacterium tuberculosis Mycobacterium bovis BCG Immunologic diseases. Allergy Maha Ahmed Al-Mozaini verfasserin aut Anthony G. Tsolaki verfasserin aut Munirah Abdul-Aziz verfasserin aut Munirah Abdul-Aziz verfasserin aut Suhair M. Abozaid verfasserin aut Suhair M. Abozaid verfasserin aut Mohammed N. Al-Ahdal verfasserin aut Ansar A. Pathan verfasserin aut Valarmathy Murugaiah verfasserin aut Evgeny M. Makarov verfasserin aut Anuvinder Kaur verfasserin aut Robert B. Sim verfasserin aut Uday Kishore verfasserin aut Lubna Kouser verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 9(2018) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:9 year:2018 https://doi.org/10.3389/fimmu.2018.00533 kostenfrei https://doaj.org/article/36f7c38f819b4a6fbc5908bb3d060aa6 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2018.00533/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
allfieldsGer	10.3389/fimmu.2018.00533 doi (DE-627)DOAJ028478444 (DE-599)DOAJ36f7c38f819b4a6fbc5908bb3d060aa6 DE-627 ger DE-627 rakwb eng RC581-607 Maha Ahmed Al-Mozaini verfasserin aut Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mycobacterium tuberculosis can proficiently enter macrophages and diminish complement activation on its cell surface. Within macrophages, the mycobacterium can suppress macrophage apoptosis and survive within the intracellular environment. Previously, we have shown that complement regulatory proteins such as factor H may interfere with pathogen–macrophage interactions during tuberculosis infection. In this study, we show that Mycobacterium bovis BCG binds properdin, an upregulator of the complement alternative pathway. TSR4+5, a recombinant form of thrombospondin repeats 4 and 5 of human properdin expressed in tandem, which is an inhibitor of the alternative pathway, was also able to bind to M. bovis BCG. Properdin and TSR4+5 were found to inhibit uptake of M. bovis BCG by THP-1 macrophage cells in a dose-dependent manner. Quantitative real-time PCR revealed elevated pro-inflammatory responses (TNF-α, IL-1β, and IL-6) in the presence of properdin or TSR4+5, which gradually decreased over 6 h. Correspondingly, anti-inflammatory responses (IL-10 and TGF-β) showed suppressed levels of expression in the presence of properdin, which gradually increased over 6 h. Multiplex cytokine array analysis also revealed that properdin and TSR4+5 significantly enhanced the pro-inflammatory response (TNF-α, IL-1β, and IL-1α) at 24 h, which declined at 48 h, whereas the anti-inflammatory response (IL-10) was suppressed. Our results suggest that properdin may interfere with mycobacterial entry into macrophages via TSR4 and TSR5, particularly during the initial stages of infection, thus affecting the extracellular survival of the pathogen. This study offers novel insights into the non-complement related functions of properdin during host–pathogen interactions in tuberculosis. complement cytokine properdin macrophage Mycobacterium tuberculosis Mycobacterium bovis BCG Immunologic diseases. Allergy Maha Ahmed Al-Mozaini verfasserin aut Anthony G. Tsolaki verfasserin aut Munirah Abdul-Aziz verfasserin aut Munirah Abdul-Aziz verfasserin aut Suhair M. Abozaid verfasserin aut Suhair M. Abozaid verfasserin aut Mohammed N. Al-Ahdal verfasserin aut Ansar A. Pathan verfasserin aut Valarmathy Murugaiah verfasserin aut Evgeny M. Makarov verfasserin aut Anuvinder Kaur verfasserin aut Robert B. Sim verfasserin aut Uday Kishore verfasserin aut Lubna Kouser verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 9(2018) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:9 year:2018 https://doi.org/10.3389/fimmu.2018.00533 kostenfrei https://doaj.org/article/36f7c38f819b4a6fbc5908bb3d060aa6 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2018.00533/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
allfieldsSound	10.3389/fimmu.2018.00533 doi (DE-627)DOAJ028478444 (DE-599)DOAJ36f7c38f819b4a6fbc5908bb3d060aa6 DE-627 ger DE-627 rakwb eng RC581-607 Maha Ahmed Al-Mozaini verfasserin aut Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mycobacterium tuberculosis can proficiently enter macrophages and diminish complement activation on its cell surface. Within macrophages, the mycobacterium can suppress macrophage apoptosis and survive within the intracellular environment. Previously, we have shown that complement regulatory proteins such as factor H may interfere with pathogen–macrophage interactions during tuberculosis infection. In this study, we show that Mycobacterium bovis BCG binds properdin, an upregulator of the complement alternative pathway. TSR4+5, a recombinant form of thrombospondin repeats 4 and 5 of human properdin expressed in tandem, which is an inhibitor of the alternative pathway, was also able to bind to M. bovis BCG. Properdin and TSR4+5 were found to inhibit uptake of M. bovis BCG by THP-1 macrophage cells in a dose-dependent manner. Quantitative real-time PCR revealed elevated pro-inflammatory responses (TNF-α, IL-1β, and IL-6) in the presence of properdin or TSR4+5, which gradually decreased over 6 h. Correspondingly, anti-inflammatory responses (IL-10 and TGF-β) showed suppressed levels of expression in the presence of properdin, which gradually increased over 6 h. Multiplex cytokine array analysis also revealed that properdin and TSR4+5 significantly enhanced the pro-inflammatory response (TNF-α, IL-1β, and IL-1α) at 24 h, which declined at 48 h, whereas the anti-inflammatory response (IL-10) was suppressed. Our results suggest that properdin may interfere with mycobacterial entry into macrophages via TSR4 and TSR5, particularly during the initial stages of infection, thus affecting the extracellular survival of the pathogen. This study offers novel insights into the non-complement related functions of properdin during host–pathogen interactions in tuberculosis. complement cytokine properdin macrophage Mycobacterium tuberculosis Mycobacterium bovis BCG Immunologic diseases. Allergy Maha Ahmed Al-Mozaini verfasserin aut Anthony G. Tsolaki verfasserin aut Munirah Abdul-Aziz verfasserin aut Munirah Abdul-Aziz verfasserin aut Suhair M. Abozaid verfasserin aut Suhair M. Abozaid verfasserin aut Mohammed N. Al-Ahdal verfasserin aut Ansar A. Pathan verfasserin aut Valarmathy Murugaiah verfasserin aut Evgeny M. Makarov verfasserin aut Anuvinder Kaur verfasserin aut Robert B. Sim verfasserin aut Uday Kishore verfasserin aut Lubna Kouser verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 9(2018) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:9 year:2018 https://doi.org/10.3389/fimmu.2018.00533 kostenfrei https://doaj.org/article/36f7c38f819b4a6fbc5908bb3d060aa6 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2018.00533/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
language	English
source	In Frontiers in Immunology 9(2018) volume:9 year:2018
sourceStr	In Frontiers in Immunology 9(2018) volume:9 year:2018
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	complement cytokine properdin macrophage Mycobacterium tuberculosis Mycobacterium bovis BCG Immunologic diseases. Allergy
isfreeaccess_bool	true
container_title	Frontiers in Immunology
authorswithroles_txt_mv	Maha Ahmed Al-Mozaini @@aut@@ Anthony G. Tsolaki @@aut@@ Munirah Abdul-Aziz @@aut@@ Suhair M. Abozaid @@aut@@ Mohammed N. Al-Ahdal @@aut@@ Ansar A. Pathan @@aut@@ Valarmathy Murugaiah @@aut@@ Evgeny M. Makarov @@aut@@ Anuvinder Kaur @@aut@@ Robert B. Sim @@aut@@ Uday Kishore @@aut@@ Lubna Kouser @@aut@@
publishDateDaySort_date	2018-01-01T00:00:00Z
hierarchy_top_id	657998354
id	DOAJ028478444
language_de	englisch
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callnumber-first	R - Medicine
author	Maha Ahmed Al-Mozaini
spellingShingle	Maha Ahmed Al-Mozaini misc RC581-607 misc complement misc cytokine misc properdin misc macrophage misc Mycobacterium tuberculosis misc Mycobacterium bovis BCG misc Immunologic diseases. Allergy Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5
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topic_title	RC581-607 Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5 complement cytokine properdin macrophage Mycobacterium tuberculosis Mycobacterium bovis BCG
topic	misc RC581-607 misc complement misc cytokine misc properdin misc macrophage misc Mycobacterium tuberculosis misc Mycobacterium bovis BCG misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc complement misc cytokine misc properdin misc macrophage misc Mycobacterium tuberculosis misc Mycobacterium bovis BCG misc Immunologic diseases. Allergy
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title	Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5
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title_full	Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5
author_sort	Maha Ahmed Al-Mozaini
journal	Frontiers in Immunology
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author_browse	Maha Ahmed Al-Mozaini Anthony G. Tsolaki Munirah Abdul-Aziz Suhair M. Abozaid Mohammed N. Al-Ahdal Ansar A. Pathan Valarmathy Murugaiah Evgeny M. Makarov Anuvinder Kaur Robert B. Sim Uday Kishore Lubna Kouser
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title_sort	human properdin modulates macrophage: mycobacterium bovis bcg interaction via thrombospondin repeats 4 and 5
callnumber	RC581-607
title_auth	Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5
abstract	Mycobacterium tuberculosis can proficiently enter macrophages and diminish complement activation on its cell surface. Within macrophages, the mycobacterium can suppress macrophage apoptosis and survive within the intracellular environment. Previously, we have shown that complement regulatory proteins such as factor H may interfere with pathogen–macrophage interactions during tuberculosis infection. In this study, we show that Mycobacterium bovis BCG binds properdin, an upregulator of the complement alternative pathway. TSR4+5, a recombinant form of thrombospondin repeats 4 and 5 of human properdin expressed in tandem, which is an inhibitor of the alternative pathway, was also able to bind to M. bovis BCG. Properdin and TSR4+5 were found to inhibit uptake of M. bovis BCG by THP-1 macrophage cells in a dose-dependent manner. Quantitative real-time PCR revealed elevated pro-inflammatory responses (TNF-α, IL-1β, and IL-6) in the presence of properdin or TSR4+5, which gradually decreased over 6 h. Correspondingly, anti-inflammatory responses (IL-10 and TGF-β) showed suppressed levels of expression in the presence of properdin, which gradually increased over 6 h. Multiplex cytokine array analysis also revealed that properdin and TSR4+5 significantly enhanced the pro-inflammatory response (TNF-α, IL-1β, and IL-1α) at 24 h, which declined at 48 h, whereas the anti-inflammatory response (IL-10) was suppressed. Our results suggest that properdin may interfere with mycobacterial entry into macrophages via TSR4 and TSR5, particularly during the initial stages of infection, thus affecting the extracellular survival of the pathogen. This study offers novel insights into the non-complement related functions of properdin during host–pathogen interactions in tuberculosis.
abstractGer	Mycobacterium tuberculosis can proficiently enter macrophages and diminish complement activation on its cell surface. Within macrophages, the mycobacterium can suppress macrophage apoptosis and survive within the intracellular environment. Previously, we have shown that complement regulatory proteins such as factor H may interfere with pathogen–macrophage interactions during tuberculosis infection. In this study, we show that Mycobacterium bovis BCG binds properdin, an upregulator of the complement alternative pathway. TSR4+5, a recombinant form of thrombospondin repeats 4 and 5 of human properdin expressed in tandem, which is an inhibitor of the alternative pathway, was also able to bind to M. bovis BCG. Properdin and TSR4+5 were found to inhibit uptake of M. bovis BCG by THP-1 macrophage cells in a dose-dependent manner. Quantitative real-time PCR revealed elevated pro-inflammatory responses (TNF-α, IL-1β, and IL-6) in the presence of properdin or TSR4+5, which gradually decreased over 6 h. Correspondingly, anti-inflammatory responses (IL-10 and TGF-β) showed suppressed levels of expression in the presence of properdin, which gradually increased over 6 h. Multiplex cytokine array analysis also revealed that properdin and TSR4+5 significantly enhanced the pro-inflammatory response (TNF-α, IL-1β, and IL-1α) at 24 h, which declined at 48 h, whereas the anti-inflammatory response (IL-10) was suppressed. Our results suggest that properdin may interfere with mycobacterial entry into macrophages via TSR4 and TSR5, particularly during the initial stages of infection, thus affecting the extracellular survival of the pathogen. This study offers novel insights into the non-complement related functions of properdin during host–pathogen interactions in tuberculosis.
abstract_unstemmed	Mycobacterium tuberculosis can proficiently enter macrophages and diminish complement activation on its cell surface. Within macrophages, the mycobacterium can suppress macrophage apoptosis and survive within the intracellular environment. Previously, we have shown that complement regulatory proteins such as factor H may interfere with pathogen–macrophage interactions during tuberculosis infection. In this study, we show that Mycobacterium bovis BCG binds properdin, an upregulator of the complement alternative pathway. TSR4+5, a recombinant form of thrombospondin repeats 4 and 5 of human properdin expressed in tandem, which is an inhibitor of the alternative pathway, was also able to bind to M. bovis BCG. Properdin and TSR4+5 were found to inhibit uptake of M. bovis BCG by THP-1 macrophage cells in a dose-dependent manner. Quantitative real-time PCR revealed elevated pro-inflammatory responses (TNF-α, IL-1β, and IL-6) in the presence of properdin or TSR4+5, which gradually decreased over 6 h. Correspondingly, anti-inflammatory responses (IL-10 and TGF-β) showed suppressed levels of expression in the presence of properdin, which gradually increased over 6 h. Multiplex cytokine array analysis also revealed that properdin and TSR4+5 significantly enhanced the pro-inflammatory response (TNF-α, IL-1β, and IL-1α) at 24 h, which declined at 48 h, whereas the anti-inflammatory response (IL-10) was suppressed. Our results suggest that properdin may interfere with mycobacterial entry into macrophages via TSR4 and TSR5, particularly during the initial stages of infection, thus affecting the extracellular survival of the pathogen. This study offers novel insights into the non-complement related functions of properdin during host–pathogen interactions in tuberculosis.
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title_short	Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5
url	https://doi.org/10.3389/fimmu.2018.00533 https://doaj.org/article/36f7c38f819b4a6fbc5908bb3d060aa6 http://journal.frontiersin.org/article/10.3389/fimmu.2018.00533/full https://doaj.org/toc/1664-3224
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author2	Maha Ahmed Al-Mozaini Anthony G. Tsolaki Munirah Abdul-Aziz Suhair M. Abozaid Mohammed N. Al-Ahdal Ansar A. Pathan Valarmathy Murugaiah Evgeny M. Makarov Anuvinder Kaur Robert B. Sim Uday Kishore Lubna Kouser
author2Str	Maha Ahmed Al-Mozaini Anthony G. Tsolaki Munirah Abdul-Aziz Suhair M. Abozaid Mohammed N. Al-Ahdal Ansar A. Pathan Valarmathy Murugaiah Evgeny M. Makarov Anuvinder Kaur Robert B. Sim Uday Kishore Lubna Kouser
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up_date	2024-07-03T17:48:18.831Z
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