Human properdin modulates macrophage: mycobacterium bovis BCG interaction via thrombospondin repeats 4 and 5

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Title: Human properdin modulates macrophage: mycobacterium bovis BCG interaction via thrombospondin repeats 4 and 5
Author(s): Al-Mozaini, MA
Tsolaki, AG
Abdul-Aziz, M
Abozaid, SM
Al-Ahdal, MN
Pathan, AA
Murugaiah, V
Makarov, EM
Kaur, A
Sim, RB
Kishore, U
Kouser, L
Item Type: Journal Article
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.
Publication Date: 8-May-2018
Date of Acceptance: 1-Mar-2018
URI: http://hdl.handle.net/10044/1/60618
DOI: https://dx.doi.org/10.3389/fimmu.2018.00533
ISSN: 1664-3224
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Immunology
Volume: 9
Copyright Statement: © 2018 Al-Mozaini, Tsolaki, Abdul-Aziz, Abozaid, Al-Ahdal, Pathan, Murugaiah, Makarov, Kaur, Sim, Kishore and Kouser. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY - https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
complement
cytokine
properdin
macrophage
Mycobacterium tuberculosis
Mycobacterium bovis BCG
phagocytosis
thrombospondin repeat
COMPLEMENT ALTERNATIVE PATHWAY
RECEPTOR-TYPE 3
TUBERCULOSIS INFECTION
PATTERN-RECOGNITION
GRANULOMA-FORMATION
NONOPSONIC BINDING
IMMUNE-RESPONSE
I REPEATS
CELLS
ACTIVATION
Mycobacterium bovis BCG
Mycobacterium tuberculosis
complement
cytokine
macrophage
phagocytosis
properdin
thrombospondin repeats
Science & Technology
Life Sciences & Biomedicine
Immunology
complement
cytokine
properdin
macrophage
Mycobacterium tuberculosis
Mycobacterium bovis BCG
phagocytosis
thrombospondin repeat
COMPLEMENT ALTERNATIVE PATHWAY
RECEPTOR-TYPE 3
TUBERCULOSIS INFECTION
PATTERN-RECOGNITION
GRANULOMA-FORMATION
NONOPSONIC BINDING
IMMUNE-RESPONSE
I REPEATS
CELLS
ACTIVATION
Publication Status: Published
Article Number: 533
Online Publication Date: 2018-05-08
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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