In a Murine Tuberculosis Model, the Absence of Homeostatic Chemokines Delays Granuloma Formation and Protective Immunity

Mycobacterium tuberculosis infection results in the generation of protective cellular immunity and formation of granulomatous structures in the lung. CXC chemokine ligand (CXCL)-13, CC chemokine ligand (CCL)-21 and CCL19 are constitutively expressed in the secondary lymphoid organs and play a dominant role in the homing of lymphocytes and dendritic cells. Although it is known that dendritic cell transport of M. tuberculosis from the lung to the draining lymph node is dependent on CCL19/CCL21, we show here that CCL19/CCL21 is also important for the accumulation of antigen-specific IFNγ-producing T cells in the lung, development of the granuloma, and control of mycobacteria. Importantly, we also show that CXCL13 is not required for generation of IFNγ responses, but is essential for the spatial arrangement of lymphocytes within granulomas, optimal activation of phagocytes and subsequent control of mycobacterial growth. Further, we show that these chemokines are also induced in the lung during the early immune responses following pulmonary M. tuberculosis infection. These results demonstrate that homeostatic chemokines perform distinct functions that cooperate to mediate effective expression of immunity against M. tuberculosis infection.