Gut Microbiota Modulates Lung Immunity Against Mycobacterial Infection

• Main Authors: Nai Chung Chang, 張乃中
• Other Authors: H. C. Lai
• Format: Others
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/67811436267881247547

碩士 === 長庚大學 === 醫學生物技術暨檢驗學系 === 100 === Adequate induction of protective immunity is essential to control virulent mycobacterial infection. Homeostasis of gut microbiota via pattern-recognition receptors (PRRs) has been linked to modulation of local and systemic immunity, whereas the role in mycobacterial pulmonary infection is unknown. Here, we show that gut microbiota is critical for regulation of lung immunity against M. kansasii-induced pulmonary infection in mice. Depleted commensal microbiota by antibiotics cocktail (ABX) or neomycin leads to mice succumbing to disseminated M. kansasii infection with extensive necrotic pulmonary damage and unlimited pathogenic neutrophil infiltration. The induced innate and adaptive immunity against M. kansasii are diminished in ABX and neomycin-treated mice. Furthermore, we identify that expression of C-type lectin (Mincle) on myeloid cells is reduced and failed to be induced in antibiotics-treated mice after M. kansasii infection. Importantly, gut flora recolonization or injection of Toll-like receptor 4 (TLR4) ligand completely rescues the impaired immunity in ABX mice. Thus, we explore a mechanism by which gut microbiota controls pulmonary anti-mycobacterial immunity.