The C-X-C motif chemokine 17 plays a minimal role during lung infection with hypervirulent Mycobacterium tuberculosis

Abstract

Abstract The C-X-C motif chemokine 17 (CXCL17) is a novel mucosal chemotactic factor for myeloid cells that displays bactericidal activity against respiratory pathogens in vitro. Although CXCL17 is constitutively expressed along the respiratory tract, its function during lung infections has not been tested in vivo. We previously showed that the CXCL17 gene is overexpressed in innate lymphoid cells (ILCs) isolated from the lung of patients with active pulmonary tuberculosis (TB). Thus, in the current study we further explored the role of CXCL17 in the defense against Mycobacterium tuberculosis (Mtb). In a mouse model of aerosol infection with the prototype W-Beijing lineage Mtb strain, hypervirulent HN878, we found that CXCL17 is actively produced at the lung during the acute and chronic stages of disease, with levels peaking at 30 days post-infection. Using in vitro infection assays, we observed that lung epithelial cells, bone marrow-derived macrophages (BMDMs), and bone marrow-derived dendritic cells (BMDCs) can become cellular sources of CXCL17 in response to Mtb. In humans, the serum levels of CXCL17 are significatively higher among individuals with latent TB infection (LTBI) than in active TB patients, suggesting a protective role. However, low serum levels of CXCL17 do not correlate with increased lung damage among active TB subjects. Furthermore, CXCL17−/− mice do not exhibit increased susceptibility to Mtb HN878 infection as compared to wild type controls. Finally, administration of exogenous recombinant CXCL17 into the airways of Mtb-infected animals does not impact their lung bacterial burden despite increased recruitment of myeloid cells to the pulmonary tissue. Our data suggest that CXCL17 plays a redundant role during TB.