Eosinophils actively participate in the host response to Mtb infection

Abstract

Mycobacterium tuberculosis (Mtb) is the leading cause of mortality worldwide due to a single infectious agent. Mtb resides in pulmonary macrophages, neutrophils and phagocytes, which are also key effector cells that limit bacterial growth. The role of other granulocytic phagocytes during Mtb infection is largely unknown. Eosinophils have comparable phagocytic function to neutrophils and an overlapping repertoire of granular contents capable of limiting bacterial growth. Here we characterized eosinophil responses to Mtb in vitro and in vivo. Eosinophils from healthy human donors responded to Mtb in vitro by CD69 up-regulation and CD62L down-regulation. Mtb induced the release of the eosinophil-specific granule proteins EDN and ECP. Mtb exposure resulted in secretion of IL-1a, TNFa, MIP-1a, MIP-1b, and IL-8. These results suggest that Mtb directly affects eosinophil degranulation, and that eosinophils are able to contribute to Mtb-driven inflammation. To investigate whether eosinophils actively participate in the cellular immune response to Mtb in vivo we followed the eosinophilic response after pulmonary Mtb infection in non-human primates. Eosinophils were significantly increased in the BAL fluid of Mtb infected rhesus macaques, providing evidence that eosinophils are being actively recruited to the lung in response to Mtb in vivo. Indeed, when we analyzed Mtb infected lung tissue from patients who had undergone lung resection, eosinophils were enriched in fibrotic TB consolidations, cavity wall and necrotic caseum. We are currently investigating the biological relevance of the eosinophilic response during Mtb infection in the mouse model. This work was supported by the intramural research programs of NIAID, NIH.