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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00533/full |
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| author | Maha Ahmed Al-Mozaini Maha Ahmed Al-Mozaini Anthony G. Tsolaki Munirah Abdul-Aziz Munirah Abdul-Aziz Suhair M. Abozaid Suhair M. Abozaid Mohammed N. Al-Ahdal Ansar A. Pathan Valarmathy Murugaiah Evgeny M. Makarov Anuvinder Kaur Robert B. Sim Uday Kishore Lubna Kouser |
| author_facet | Maha Ahmed Al-Mozaini Maha Ahmed Al-Mozaini Anthony G. Tsolaki Munirah Abdul-Aziz Munirah Abdul-Aziz Suhair M. Abozaid Suhair M. Abozaid Mohammed N. Al-Ahdal Ansar A. Pathan Valarmathy Murugaiah Evgeny M. Makarov Anuvinder Kaur Robert B. Sim Uday Kishore Lubna Kouser |
| author_sort | Maha Ahmed Al-Mozaini |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T20:01:59Z |
| format | Article |
| id | doaj.art-36f7c38f819b4a6fbc5908bb3d060aa6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T20:01:59Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-36f7c38f819b4a6fbc5908bb3d060aa62022-12-22T02:32:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-05-01910.3389/fimmu.2018.00533292498Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5Maha Ahmed Al-Mozaini0Maha Ahmed Al-Mozaini1Anthony G. Tsolaki2Munirah Abdul-Aziz3Munirah Abdul-Aziz4Suhair M. Abozaid5Suhair M. Abozaid6Mohammed N. Al-Ahdal7Ansar A. Pathan8Valarmathy Murugaiah9Evgeny M. Makarov10Anuvinder Kaur11Robert B. Sim12Uday Kishore13Lubna Kouser14College of Health and Life Sciences, Brunel University London, London, United KingdomDepartment of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaCollege of Health and Life Sciences, Brunel University London, London, United KingdomCollege of Health and Life Sciences, Brunel University London, London, United KingdomDepartment of Biochemistry, Oxford University, Oxford, United KingdomCollege of Health and Life Sciences, Brunel University London, London, United KingdomDepartment of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaCollege of Health and Life Sciences, Brunel University London, London, United KingdomCollege of Health and Life Sciences, Brunel University London, London, United KingdomCollege of Health and Life Sciences, Brunel University London, London, United KingdomCollege of Health and Life Sciences, Brunel University London, London, United KingdomDepartment of Biochemistry, Oxford University, Oxford, United KingdomCollege of Health and Life Sciences, Brunel University London, London, United KingdomCollege of Health and Life Sciences, Brunel University London, London, United KingdomMycobacterium 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.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00533/fullcomplementcytokineproperdinmacrophageMycobacterium tuberculosisMycobacterium bovis BCG |
| spellingShingle | Maha Ahmed Al-Mozaini Maha Ahmed Al-Mozaini Anthony G. Tsolaki Munirah Abdul-Aziz Munirah Abdul-Aziz Suhair M. Abozaid Suhair M. Abozaid Mohammed N. Al-Ahdal Ansar A. Pathan Valarmathy Murugaiah Evgeny M. Makarov Anuvinder Kaur Robert B. Sim Uday Kishore Lubna Kouser Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5 Frontiers in Immunology complement cytokine properdin macrophage Mycobacterium tuberculosis Mycobacterium bovis BCG |
| title | Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5 |
| title_full | Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5 |
| title_fullStr | Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5 |
| title_full_unstemmed | Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5 |
| title_short | Human Properdin Modulates Macrophage: Mycobacterium bovis BCG Interaction via Thrombospondin Repeats 4 and 5 |
| title_sort | human properdin modulates macrophage mycobacterium bovis bcg interaction via thrombospondin repeats 4 and 5 |
| topic | complement cytokine properdin macrophage Mycobacterium tuberculosis Mycobacterium bovis BCG |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00533/full |
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