IL-23 is required for long-term control of Mycobacterium tuberculosis and B cell follicle formation in the infected lung. (150.1)

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Abstract IL-23 is required for effective IL-17 responses to aerosol infection with Mycobacterium tuberculosis (Mtb), however it does not appear to impact early control of bacterial growth in the lung. By extending the time course of infection using mice deficient for the p19 component of the IL-23 cytokine, we report that there is increased bacterial growth in the lungs of these mice compared to wild type infected mice. This increased bacterial growth is associated with decreased maintenance of B cell follicles within lungs of infected mice. While mRNA expression for molecules associated with limiting bacterial growth such as Interferon gamma (IFNγ) were equivalent between wild type and IL-23p19 deficient mice, reduced expression of both IL-17 and IL-22 mRNA was observed in IL-23p19 deficient Mtb-infected lungs. Importantly, we show that in mice deficient for IL-23p19, B cell follicle size was reduced during chronic Mtb infection and this was temporally associated with the increased bacterial burden. In mice deficient in the IL-17 receptor (IL-17R), B cell follicle generation was affected early in infection whereas the absence of IL-22 influenced the size of B cell follicles in the mid-term. Interestingly, the absence of IL-22 or IL-17R alone did not impact bacterial control. Thus, we show novel data that while IL-23 is required for long term control of Mtb growth in the lung, there is a compensatory effect of IL-22 and IL-17 during tuberculosis.