| Summary: | 碩士 === 國立成功大學 === 臨床醫學研究所 === 101 === Tuberculosis (TB) is a worldwide infectious disease which kills more than 1.5 million people every year. The pathogen of TB, Mycobacterium tuberculosis (M. tb), is an aerosol infectious pathogen which can infect macrophages and initiate local inflammation in the host lung, which recruits innate immune cells (including other macrophages, monocytes and polymorphonuclear cells (PMNs)) and lymphocytes to form granulomas. In addition, mycobacterial infection can also induce tertiary lymphoid tissue (TLT) formation, which is effective to activate adaptive immune response to control pathogen invasion. Within the immune response against M. tb infection, NADPH oxidase-produced reactive oxygen species (ROS) plays an important role. Previous studies have shown that mice with mutant p47phox (Ncf1-/-), which leads to lack of functional NADPH oxidase 2 (NOX2) and hence defective ROS production by leukocytes, are susceptible to mycobacterial infection. However, the specific roles of how leukocytes’ ROS resist mycobacteria invasion are still unclear. In this study, we intratracheally infected both wild type mice and Ncf1-/- mice with M. bovis bacillus Calmette-Guérin (BCG), and found that cell infiltration, proinflammatory cytokines production, granuloma number and bacterial load in the lungs of Ncf1-/- mice were increased when compared with WT mice. In addition, the numbers of neutrophils in Ncf1-/- mice were extremely higher than WT mice, and lead to forming the granuloma in Ncf1-/- mice. Moreover, Ncf1-/- mice had impaired ability to form well-organized tertiary lymphoid tissue after BCG infection due to reduced TLT-related chemokines production. In conclusion, our results showed that leukocyte-produced ROS can effectively eradicate mycobacterial infection and modulate both granuloma and TLT formation.
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