The compositional organization of Mycobacterium tuberculosis granulomas is analogous to ectopic lymphoid organs (40.2)

Abstract

Abstract Secondary lymphoid organs (SLOs) are integral in generating an effective adaptive immune response. Homing of cells to SLOs is a result of homeostatic chemokines, such as CXCL13. CXCL13, the ligand for CXCR5, is responsible for the recruitment of germinal center cells including B cells, T follicular helper (Tfh) cells and follicular dendritic cells (FDCs). Recently, CXCL13 has been reported in the lungs of mice following infection with Mycobacterium tuberculosis (Mtb). We found CXCL13 to be localized within the granuloma in both mice and human lungs as early as day 22 post infection in mice. In addition, we found Tfh cells, B cells, and FDCs localized within the granuloma of mice and humans. Recruitment of Tfh cells was seen in the draining lymph nodes by day 15 with accumulation in the lung by day 21 in Mtb infected mice. Infiltration of Tfh cells in the lung coincided with an increase in mRNA for known Tfh factors such as ICOS, BCL-6, IL-6 and IL-21, which followed upregulation of CXCL13 at day 18. Interestingly, another CXCR5+ population infiltrated the lung prior to accumulation of Tfh cells. These cells accumulate at day 12 and express surface markers suggestive of a monocyte lineage. Further, CXCR5-/- mice are more susceptible to Mtb infection by day 21. Our data suggest that the Mtb granuloma may function as an ectopic lymphoid organ, which may require involvement of CXCR5+ cells to elicit protective immunity.