CpsA mediates infection of recruited lung myeloid cells by Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) possesses an arsenal of virulence factors to evade host immunity. Previously, we showed that the Mtb protein CpsA, which protects Mtb against the host NADPH oxidase, is required in mice during the first 3 weeks of infection but is thereafter dispensable for full virulence. Using flow cytometry, we find that ΔcpsA Mtb is retained in alveolar macrophages, impaired in recruiting and disseminating into monocyte-derived cells, and more likely to be localized in airway cells than wild-type Mtb. The lungs of ΔcpsA-infected mice also have markedly fewer antigen-specific T cells, indicating a delay in adaptive immunity. Thus, we conclude that CpsA promotes dissemination of Mtb from alveolar macrophages and the airways and generation of an adaptive immune response. Our studies of ΔcpsA Mtb show that a more effective innate immune response against Mtb can be undermined by a corresponding delay in the adaptive immune response.