Sex-specific impact of B cell-derived IL-10 on tuberculosis resistance

Due to the historical dogma that host defense against intracellular pathogens is primarily mediated by cell-mediated immunity, B cells have long been considered unimportant in providing protection against Mycobacterium tuberculosis (Mtb) and remained understudied for decades. However, emerging evidence highlights the multifaceted role of B cells in tuberculosis (TB) immunity. B cells accumulate at the site of infection in both animal models and human TB patients, suggesting a potential link to protective immunity. Still, the diverse roles of B cells in TB immunity are still being unraveled. In addition to producing antibodies, B cells secrete a wide range of cytokines that can influence the local immune response. In this study, we focused on the relevance of interleukin 10 (IL-10)-secreting B cells in the long-term control of the Mtb Beijing strain HN878.

B cell-specific IL-10 expression was assessed in IL-10 transcriptional reporter (Vert-X) mice following Mtb infection. To investigate the role of B cell-derived IL-10 in TB immunity, both male and female mice with a targeted knockout of IL-10 in B cells (IL-10^flox/CD19^cre) were infected with Mtb HN878. Disease progression, control of bacterial replication, and immunological changes were monitored throughout the course of infection.

B cells contribute to IL-10 production in the Mtb-infected lung in both sexes, with CD138⁺ plasma cells serving as the primary source of B cell-derived IL-10. Mice lacking B cell-derived IL-10 exhibited increased resistance to aerosol Mtb infection, demonstrated by a delayed onset of clinical symptoms and prolonged survival. Notably, this effect was significantly more pronounced in males compared to females, and was associated with male-specific immune alterations.

Our research highlights a previously unrecognized sex-specific regulatory role of B cell-derived IL-10 during Mtb infection.