Partial redundancy of the pattern recognition receptors, scavenger receptors, and C-type lectins for the long-term control of Mycobacterium tuberculosis infection

Nathalie Court, Virginie Vasseur, Rachel Vacher, Cécile Frémond, Yury Shebzukhov, Vladimir V. Yeremeev, Isabelle Maillet, Sergei A. Nedospasov, Siamon Gordon, Padraic G. Fallon, Hiroshi Suzuki, Bernhard Ryffel, Valérie F.J. Quesniaux

Research output: Contribution to journalJournal Article peer-review

79 Scopus citations

Abstract

Mycobacterium tuberculosis is recognized by multiple pattern recognition receptors involved in innate immune defense, but their direct role in tuberculosis pathogenesis remains unknown. Beyond TLRs, scavenger receptors (SRs) and C-type lectins may play a crucial role in the sensing and signaling of pathogen motifs, as well as contribute to M. tuberculosis immune evasion. In this study, we addressed the relative role and potential redundancy of these receptors in the host response and resistance to M. tuberculosis infection using mice deficient for representative SR, C-type lectin receptor, or seven transmembrane receptor families.We show that a single deficiency in the class A SR, macrophage receptor with collagenous structure, CD36, mannose receptor, specific ICAM-3 grabbing nonintegrin-related, or F4/80 did not impair the host resistance to acute or chronic M. tuberculosis infection in terms of survival, control of bacterial clearance, lung inflammation, granuloma formation, and cytokine and chemokine expression. Double deficiency for the SRs classASR types I and II plus CD36 or for the C-type lectins mannose receptor plus specific ICAM-3 grabbing nonintegrin-related had a limited effect on macrophage uptake of mycobacteria andTNFresponse and on the long-term control of M. tuberculosis infection. By contrast, mice deficient in the TNF, IL-1, or IFN-γ pathway were unable to control acute M. tuberculosis infection. In conclusion, we document a functional redundancy in the pattern recognition receptors, which might cooperate in a coordinated response to sustain the full immune control of M. tuberculosis infection, in sharp contrast with the nonredundant, essential role of the TNF, IL-1, or IFN-γ pathway for host resistance to M. tuberculosis.

Original languageEnglish
Pages (from-to)7057-7070
Number of pages14
JournalJournal of Immunology
Volume184
Issue number12
DOIs
StatePublished - 15 06 2010
Externally publishedYes

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