PT  - JOURNAL ARTICLE
AU  - Carolina G. Dolislager
AU  - Sean M. Callahan
AU  - Dallas R. Donohoe
AU  - Jeremiah G. Johnson
TI  - <em>Campylobacter jejuni</em> induces differentiation of human neutrophils to the CD16<sup>hi</sup>/CD62L<sup>lo</sup> subtype which possess cancer promoting activities
AID  - 10.1101/2022.01.28.478176
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.28.478176
4099  - http://biorxiv.org/content/early/2022/01/28/2022.01.28.478176.short
4100  - http://biorxiv.org/content/early/2022/01/28/2022.01.28.478176.full
AB  - 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 jejuni induced differentiation of human neutrophils into the hypersegmented, CD16hi/CD62Llo subtype. In addition, we investigated whether C. jejuni-dependent differentiation of this neutrophil subtype induced cancer promoting activities of human T cells and colonocytes, which were observed in other studies of hypersegmented, CD16hi/CD62Llo neutrophils. We found that C. jejuni causes a significant shift in human neutrophil populations to the hypersegmented, 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 of the T cell receptor (TCRζ), which was restored upon supplementation with exogenous L-arginine. In addition, incubation of C. jejuni-infected neutrophils with human colonocytes resulted in increased HIF-1α stabilization and NF-κB 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 expression in T cells, could result in the promotion of colorectal tumorigenesis during infection with C. jejuni.Competing Interest StatementThe authors have declared no competing interest.