Faculty Opinions recommendation of Long-term control of Mycobacterium bovis BCG infection in the absence of Toll-like receptors (TLRs): investigation of TLR2-, TLR6-, or TLR2-TLR4-deficient mice.

ABSTRACT Live mycobacteria have been reported to signal through both Toll-like receptor 2 (TLR2) and TLR4 in vitro. Here, we investigated the role of TLR2 in the long-term control of the infection by the attenuated Mycobacterium, Mycobacterium bovis BCG, in vivo. We sought to determine whether the reported initial defect of bacterial control (K. A. Heldwein et al., J. Leukoc. Biol. 74:277-286, 2003) resolved in the chronic phase of BCG infection. Here we show that TLR2-deficient mice survived a 6-month infection period with M. bovis BCG and were able to control bacterial growth. Granuloma formation, T-cell and macrophage recruitment, and activation were normal. Furthermore, the TLR2 coreceptor, TLR6, is also not required since TLR6-deficient mice were able to control chronic BCG infection. Finally, TLR2-TLR4-deficient mice infected with BCG survived the 8-month observation period. Interestingly, the adaptive response of TLR2- and/or TLR4-deficient mice seemed essentially normal on day 14 or 56 after infection, since T cells responded normally to soluble BCG antigens. In conclusion, our data demonstrate that TLR2, TLR4, or TLR6 are redundant for the control of M. bovis BCG mycobacterial infection.

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Mycobacterium bovis BCG Toll-Like Receptors 2 and 4 Cooperation Increases the Innate Epithelial Immune Response

Archives of Medical Research ◽

10.1016/j.arcmed.2007.06.019 ◽

2008 ◽

Vol 39 (1) ◽

pp. 33-39 ◽

Cited By ~ 15

Author(s):

Patricia Méndez-Samperio ◽

Laura Belmont ◽

Elena Miranda

Keyword(s):

Immune Response ◽

Mycobacterium Bovis ◽

Toll Like Receptors ◽

Mycobacterium Bovis Bcg

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Chronic pneumonia despite adaptive immune response to Mycobacterium bovis BCG in MyD88-deficient mice

Laboratory Investigation ◽

10.1038/labinvest.3700149 ◽

2004 ◽

Vol 84 (10) ◽

pp. 1305-1321 ◽

Cited By ~ 25

Author(s):

Delphine M Nicolle ◽

Xavier Pichon ◽

André Bouchot ◽

Isabelle Maillet ◽

François Erard ◽

...

Keyword(s):

Immune Response ◽

Mycobacterium Bovis ◽

Adaptive Immune Response ◽

Mycobacterium Bovis Bcg ◽

Adaptive Immune ◽

Chronic Pneumonia ◽

Deficient Mice

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Correction of Defective Host Response to Mycobacterium Bovis BCG Infection in TNF-Deficient Mice by Bone Marrow Transplantation

Laboratory Investigation ◽

10.1038/labinvest.3780094 ◽

2000 ◽

Vol 80 (6) ◽

pp. 901-914 ◽

Cited By ~ 40

Author(s):

Muazzam Jacobs ◽

Mike W Marino ◽

Najmeeyah Brown ◽

Brian Abel ◽

Linda-Gail Bekker ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Mycobacterium Bovis ◽

Marrow Transplantation ◽

Host Response ◽

Mycobacterium Bovis Bcg ◽

Deficient Mice

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Oral delivery of lipid-encapsulated Mycobacterium bovis BCG extends survival of the bacillus in vivo and induces a long-term protective immune response against tuberculosis

Vaccine ◽

10.1016/j.vaccine.2005.11.017 ◽

2006 ◽

Vol 24 (12) ◽

pp. 2071-2078 ◽

Cited By ~ 43

Author(s):

F.E. Aldwell ◽

M.L. Cross ◽

C.E. Fitzpatrick ◽

M.R. Lambeth ◽

G.W. de Lisle ◽

...

Keyword(s):

Immune Response ◽

Mycobacterium Bovis ◽

Oral Delivery ◽

Protective Immune Response ◽

Mycobacterium Bovis Bcg

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Mycobacterium bovis BCG promotes IL-10 expression by establishing a SYK/PKCα/β positive autoregulatory loop that sustains STAT3 activation

Pathogens and Disease ◽

10.1093/femspd/ftz032 ◽

2019 ◽

Vol 77 (3) ◽

Author(s):

Tomás Villaseñor ◽

Edgardo Madrid-Paulino ◽

Rafael Maldonado-Bravo ◽

Leonor Pérez-Martínez ◽

Gustavo Pedraza-Alva

Keyword(s):

Mycobacterium Bovis ◽

Feedback Loop ◽

Expression Profiles ◽

Adaptive Immune Response ◽

Gene Expression Profiles ◽

Cytokine Gene Expression ◽

Mycobacterium Bovis Bcg ◽

Adaptive Immune

ABSTRACT Mycobacterium ensures its survival inside macrophages and long-term infection by subverting the innate and adaptive immune response through the modulation of cytokine gene expression profiles. Different Mycobacterium species promote the expression of TGFβ and IL-10, which, at the early stages of infection, block the formation of the phagolysosome, thereby securing mycobacterial survival upon phagocytosis, and at later stages, antagonize IFNγ production and functions. Despite the key role of IL-10 in mycobacterium infection, the signal transduction pathways leading to IL-10 expression in infected macrophages are poorly understood. Here, we report that Mycobacterium bovis BCG promotes IL-10 expression and cytokine production by establishing a SYK/PKCα/β positive feedback loop that leads to STAT3 activation.

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