<i>Mycobacterium tuberculosis</i>Infection in Complement Receptor 3-Deficient Mice

Hu, Chenggang; Mayadas-Norton, Tanya; Tanaka, Katie; Chan, John; Salgame, Padmini

doi:10.4049/jimmunol.165.5.2596

Cited by 80 publications

(58 citation statements)

References 30 publications

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“…These groups found that macrophages from CR3-deficient mice phagocytized significantly less M. tuberculosis cells in the presence (21,26) and absence (26) of serum than macrophages from wild-type mice. However, they found no difference in infection or disease outcome in CR3-deficient mice infected with M. tuberculosis compared to wild-type mice.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterial Protein HbhA Binds Human Complement Component C3

2001

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Mycobacterium tuberculosis andMycobacterium tuberculosis, the causative agent of tuberculosis, is a facultative intracellular pathogen that can be phagocytosed by human mononuclear phagocytes and survive and replicate inside these cells. This bacterium can bind to several types of receptors on the surface of mononuclear phagocytes (recently reviewed by Ernst [14]), including complement receptors (10,20,41,42,44,47). Complement receptor one (CR1) (CD35) is a single-chain glycoprotein that binds complement fragments C3b and C4b (23). CR3 (CD11b/CD18) and CR4 (CD11c/CD18) are heterodimers belonging to the leukocyte ␤ 2 -integrin family. These two receptors bind complement fragment C3bi and also contain a polysaccharide binding site (2, 24). M. tuberculosis can bind to the complement receptors via both complement-dependent and -independent pathways (10,20,41,42,44,47) and is subsequently phagocytosed by the phagocytic cell. The presence of human serum containing active complement components was found to enhance the binding of M. tuberculosis to CR1, CR3, and CR4 on the surface of human monocytes and monocyte-derived macrophages (MDMS) (20,41,42). Complement component C3 was identified as the major component in human serum involved in enhancing the adherence and uptake of M. tuberculosis by mononuclear phagocytes (42).Mycobacterium avium, a causative agent of opportunistic infections in immunocompromised individuals such as AIDS patients, is also a facultative intracellular pathogen that is able to survive and replicate in mononuclear phagocytes. M. avium is able to bind to several types of receptors on monocytes and macrophages in both the presence and absence of serum, including CR1 and CR3 (6, 7, 37). The presence of normal human serum (NHS) significantly enhances the adherence and phagocytosis of M. avium by MDMs and monocytes (7, 45), and C3 was found to be an important opsonin for the adherence and uptake of M. avium by MDMs (7).C3-binding molecules on the surface of several intracellular pathogens have been identified. These molecules include major outer membrane protein (MOMP) from Legionella pneumophila (3), MOMP from Chlamydia trachomatis (17), lipophosphoglycan from Leishmania major promastigotes (35), gp63 from Leishmania mexicana promastigotes (39), gp72 from Trypanosoma cruzi epimastigotes (22), and phenolic glycolipid-1 from Mycobacterium leprae (43). In this study, we identified a C3-binding protein in M. tuberculosis, M. avium, and Mycobacterium smegmatis using a C3 ligand affinity blot protocol and further characterized these proteins in M. tuberculosis and M. avium. MATERIALS AND METHODSBacterial strains and growth conditions. M. tuberculosis H37Rv (ATCC 27294) was purchased from the American Type Culture Collection (ATCC). M. avium ATCC 49601 was provided by C. Jagganath at the University of Texas-Houston Medical School, and M. smegmatis mc 2 155 was provided by W. R. Jacobs at the Albert Einstein College of Medicine. Escherichia coli SURE2, E. coli TOPP3, and E. coli BL21(DE3) pLysS were obtained...

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Section: Discussionmentioning

confidence: 99%

Mycobacterial Protein HbhA Binds Human Complement Component C3

2001

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“…5e). Furthermore, CR3-deficient mice mount normal Th1 responses to Mycobacterium tuberculosis (41). Second, the anti-CR3 Ab used in the present study induces a calcium flux in exposed DCs (Fig.…”

Section: Discussionmentioning

confidence: 99%

Antibodies to Complement Receptor 3 Treat Established Inflammation in Murine Models of Colitis and a Novel Model of Psoriasiform Dermatitis

León

Contractor

Fuss

et al. 2006

The Journal of Immunology

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Prior studies indicated the ability of Abs to complement receptor 3 (CR3, CD11b/CD18) to suppress the production of IL-12 from immune cells. Therefore, we tested the ability of an anti-CR3 Ab (clone M1/70) to treat established IL-12-dependent Th1-mediated inflammation in murine models. Systemic administration of anti-CR3 significantly ameliorated established intestinal inflammation following the intrarectal administration of trinitrobenzene sulfonic acid (TNBS-colitis), as well as colitis and skin inflammation in C57BL/10 RAG-2−/− mice reconstituted with CD4+CD45RBhigh T cells. The hyperproliferative skin inflammation in this novel murine model demonstrated many characteristics of human psoriasis, and was prevented by the adoptive transfer of CD45RBlow T cells. In vitro and in vivo studies suggest that anti-CR3 treatment may act, at least in part, by directly inhibiting IL-12 production by APCs. Administration of anti-CR3 may be a useful therapeutic approach to consider for the treatment of inflammatory bowel disease and psoriasis in humans.

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“…take advantage of CR3 function to avoid bacterial killing (38). The engagement of CR3 by Mycobacterium tuberculosis did not affect its intracellular survival (39) and CR3 is not involved in the outcome of M. tuberculosis infection (40). The aggregation substance of Enterococcus faecalis interacts with CR3, causes increased bacterial uptake, and prevents microbicidal activity of macrophages (41).…”

Section: Discussionmentioning

confidence: 99%

Coxiella burnetii Avoids Macrophage Phagocytosis by Interfering with Spatial Distribution of Complement Receptor 3

Capo

Moynault

Collette

et al. 2003

The Journal of Immunology

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Phagocytosis is a highly localized event requiring the formation of spatially and temporally restricted signals. Numerous microorganisms have taken advantage of this property to invade host cells. Coxiella burnetii, the agent of Q fever, is an obligate intracellular bacterium that has developed a survival strategy in macrophages based on subversion of receptor-mediated phagocytosis. The uptake of C. burnetii is mediated by αvβ3 integrin and is restricted by impaired cross-talk of αvβ3 integrin and complement receptor 3 (CR3) (CD11b/CD18). In this study, we showed that CR3 molecules remained outside the pseudopodal extensions induced by C. burnetii in THP-1 monocytes, although αvβ3 integrin was present in the pseudopods. Chemoattractants such as RANTES restored CR3 localization to the front of pseudopodal extensions and increased C. burnetii phagocytosis, demonstrating that the localization of CR3 is critical for bacterial uptake. In addition, monocyte activation due to the expression of HIV-1 Nef protein also restored CR3-mediated phagocytosis of C. burnetii by allowing CR3 redistribution toward bacterial-induced pseudopods. The redistribution of CR3 and increased C. burnetii phagocytosis in THP-1 cells stimulated by RANTES or expressing Nef were associated with the inhibition of intracellular replication of C. burnetii. Hence, the localization of CR3 is critical for bacterial phagocytosis and also for the control of bacterial replication. This study describes a nonpreviously reported strategy of phagocytosis subversion by intracellular pathogens based on altered localization of monocyte receptors.

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Mycobacterium tuberculosisInfection in Complement Receptor 3-Deficient Mice

Cited by 80 publications

References 30 publications

Mycobacterial Protein HbhA Binds Human Complement Component C3

Mycobacterial Protein HbhA Binds Human Complement Component C3

Antibodies to Complement Receptor 3 Treat Established Inflammation in Murine Models of Colitis and a Novel Model of Psoriasiform Dermatitis

Coxiella burnetii Avoids Macrophage Phagocytosis by Interfering with Spatial Distribution of Complement Receptor 3

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