Prior appendectomy attenuates the immune protective efficacy of BCG vaccination against Mycobacterium tuberculosis infection

Abstract

Cecal appendix is a unique niche for commensal bacteria, and has been considered the primary site for immunoglobulin A production. Yet its immune function in anti-infection immunity has not been fully understood. In order to elucidate whether cecal patch (CeP), the murine version of appendix, would influence the immune response induced by Mycobacterium tuberculosis (M. tb) and the vaccine effect of Bacillus Calmette-Guérin (BCG), BALB/c mice at 4 weeks of age received appendectomy or sham operation and recovered for 2 weeks before intranasal infection with 2 × 10⁷ CFU Mycobacterium tuberculosis H37Ra. Appendectomy of mice led to a reduction in lung macrophage numbers 7 days post infection (p. i.), and aggravated lung immunohistopathology 4 weeks p. i.. Appendectomized mice vaccinated with 5 × 10⁶ CFU BCG exhibited attenuated BCG-specific serum IgG, reduced lung/splenic IFN-γ⁺ T response, and weakened T proliferation and cytotoxicity, and eventually worsened lung pathology compared to sham operated mice. Mechanistically, we found that appendectomized mice at a young age (4 weeks) had an attenuated maturation of mesenteric lymph node (MLN) conventional dendritic cells (cDCs), which accounted for the impaired systemic IFN-γ⁺ T response and cytotoxicity against M. tb. Our data suggest that intact appendix maintain intestinal DC maturation and systemic Th1 induction against M. tb and has an assistant role in increasing immune efficiency of BCG vaccine.