Role of secreted IgM in regulating the host response to Mycobacterium tuberculosis

Abstract

Abstract B cell aggregates, which display characteristics of germinal center reactions, are a prominent feature in the lungs of Mycobacterium tuberculosis (Mtb)-infected hosts. Using the B cell-deficient mouse strain μMT, we have previously shown that B cells are required for optimal protection against aerosol Mtb infection. μMT mice display exacerbated lung granulomatous inflammation during acute tuberculosis (TB), and this can be ameliorated by adoptive transfer of B cells or treatment with immune serum, suggesting a role for immunoglobulin in modulating the local lung response to Mtb. To investigate the role of antibody in a protective host response to Mtb, we utilized mice deficient in various immunoglobulins. Mice unable to secrete IgM (μS−/−) were more susceptible to aerosol Mtb infection than those lacking all other immunoglobulin isotypes, and displayed increased mortality during chronic TB. Relative to wild-type (WT) mice, Mtb-infected μS−/− mice had fewer lymphoid aggregates and a delayed granulomatous response in the lungs, despite having greater numbers of activated pulmonary CD4+ T cells. Treatment of μS−/− mice with immune serum (derived from Mtb-infected WT mice) during acute infection, led to increased lymphoid aggregates and plasma cells in the lungs, more pulmonary infiltrate, a concomitant decrease in the lung bacterial burden, and ultimately delayed the onset of death of μS−/− mice during chronic TB. These data suggest IgM plays an important role in controlling Mtb infection by orchestrating local granulomatous responses in the lungs, which leads to improved host survival during the chronic phase of infection.