Neutrophil Subtype Differentiation in Campylobacter jejuni Infection and Its Impact on T cells and Colonic Epithelial Cells

The discovery of neutrophil subtypes has expanded what is known about neutrophil functions, yet there is still much to learn about the role of these subtypes during bacterial infection. We investigated whether Campylobacter jejuniinduced differentiation of human neutrophils into the hypersegmented, CD16^hi/CD62L^lo[CD16hi/CD62Llo] subtype. In addition, we investigated whether C. jejuni-dependent differentiation of this neutrophil subtype induced cancer promoting activities ofhuman T cells and colonocytes, whichwere observed in other studies of hypersegmented, CD16^hi/CD62L^lo[CD16hi/CD62Llo] neutrophils. We found that C. jejunicauses a significant shift in human neutrophil populations to the hypersegmented, CD16^hi/CD62L^lo[CD16hi/CD62Llo] subtype and that those populations exhibit delayed apoptosis, elevated arginase-1 expression, and increased reactive oxygen species production. Furthermore, incubation of C. jejuni-infected neutrophils with human T cells resulted in decreased expression of the ζ-chain [zeta-chain] of the T cell receptor (TCRζ) [TCRzeta], which wasrestored upon supplementation with exogenous L-arginine. In addition, incubation of C. jejuni-infected neutrophils with human colonocytes resulted in increased HIF-1α [HIF-1alpha] stabilization and NF-κB [NF-kappaB] activation in those colonocytes, which may result in the upregulation of pro-tumorigenic genes. This response, coupled with the ability of C. jejuni-infected neutrophils to suppress TCRζ [TCRzeta] expression in T cells, could result in the promotion of colorectal tumorigenesis during infection with C. jejuni.