TLR–Dependent Control of Francisella tularensis Infection and Host Inflammatory Responses

摘要: BACKGROUND Francisella tularensis is the causative agent of tularemia and classified as a Category A select agent. Recent studies have implicated TLR2 critical element in host protective response to F. infection, but questions remain about whether signaling dominates all circumstances with species PAMPs are predominantly recognized by TLR2/TLR1 or TLR2/TLR6. To address these questions, we explored role Toll-like receptors (TLRs) infections Live Vaccine Strain (LVS) subspecies (subsp.) novicida vivo. METHODOLOGY/PRINCIPAL FINDINGS C57BL/6 (B6) control mice TLR- MyD88-deficient were infected intranasally (i.n.) intradermally (i.d.) LVS subsp. novicida. B6 survived >21 days following infection both routes survival TLR1(-/-), TLR4(-/-), TLR6(-/-) i.n. was equivalent controls. Survival TLR2(-/-) MyD88(-/-) mice, however, significantly reduced compared regardless route tularensis. also showed increased bacterial burdens lungs, liver, spleen controls infection. Primary macrophages from impaired ability secrete TNF other pro-inflammatory cytokines upon ex vivo LVS. expression demonstrated analysis bronchoalveolar lavage fluid situ immunofluorescent staining. CONCLUSIONS/SIGNIFICANCE We conclude that MyD88, not TLR4, play roles innate immune subspecies. Moreover, through does depend exclusively on TLR1 TLR6 during