title: Partial redundancy of the pattern recognition receptors, scavenger receptors, and C-type lectins for the long-term control of Mycobacterium tuberculosis infection.
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 class A SR 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 and TNF response and on the long-term control of M. tuberculosis infection. By contrast, mice deficient in the TNF, IL-1, or IFN-gamma 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-gamma pathway for host resistance to M. tuberculosis.
authors.affiliation: University of Orleans and National Center for Scientific Research UMR6218, Molecular Immunology and Embryology, Orleans, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Court
authors.forename: Virginie
authors.initials: V
authors.lastname: Vasseur
authors.forename: Rachel
authors.initials: R
authors.lastname: Vacher
authors.forename: Cécile
authors.initials: C
authors.lastname: Frémond
authors.forename: Yury
authors.initials: Y
authors.lastname: Shebzukhov
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Yeremeev
authors.forename: Isabelle
authors.initials: I
authors.lastname: Maillet
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Nedospasov
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Valérie F J
authors.initials: VF
authors.lastname: Quesniaux
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009169:Mycobacterium tuberculosis / Q000276:immunology; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051116:Receptors, Scavenger / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D007375:Interleukin-1; D037181:Lectins, C-Type; D051192:Receptors, Pattern Recognition; D051116:Receptors, Scavenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma