creators_name: Farr, Dustin creators_name: Nag, Dhrubajyoti creators_name: Chazin , Walter J creators_name: Harrison, Simone creators_name: Thummel , Ryan creators_name: Luo , Xixia creators_name: Raychaudhuri, Saumya creators_name: Withey, Jeffrey H type: article datestamp: 2022-07-20 06:44:52 lastmod: 2022-07-20 06:44:52 metadata_visibility: show title: Neutrophil-Associated Responses to Vibrio cholerae Infection in a Natural Host Model ispublished: pub subjects: QR keywords: IL-8; Vibrio cholerae; calprotectin; cholera; innate immunity; neutrophils; zebrafish note: The copyright of this article belongs to ASM abstract: Vibrio cholerae, the cause of human cholera, is an aquatic bacterium found in association with a variety of animals in the environment, including many teleost fish species. V. cholerae infection induces a proinflammatory response followed by a noninflammatory convalescent phase. Neutrophils are integral to this early immune response. However, the relationship between the neutrophil-associated protein calprotectin and V. cholerae has not been investigated, nor have the effects of limiting transition metals on V. cholerae growth. Zebrafish are useful as a natural V. cholerae model as the entire infectious cycle can be recapitulated in the presence of an intact intestinal microbiome and mature immune responses. Here, we demonstrate that zebrafish produce a significant neutrophil, interleukin 8 (IL-8), and calprotectin response following V. cholerae infection. Bacterial growth was completely inhibited by purified calprotectin protein or the chemical chelator N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN), but growth was recovered by the addition of the transition metals zinc and manganese. The expression of downstream calprotectin targets was also significantly increased in the zebrafish. These findings illuminate the role of host calprotectin in combating V. cholerae infection. Inhibition of V. cholerae growth through metal limitation may provide new approaches in the development of anti-V. cholerae therapeutics. This study also establishes a major role for calprotectin in combating infectious diseases in zebrafish. date: 2022-03-17 date_type: published publication: Infection and immunity volume: 90 number: 3 publisher: ASM refereed: TRUE issn: 0019-9567 official_url: https://journals.asm.org/doi/10.1128/iai.00466-21?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed citation: Farr, Dustin and Nag, Dhrubajyoti and Chazin , Walter J and Harrison, Simone and Thummel , Ryan and Luo , Xixia and Raychaudhuri, Saumya and Withey, Jeffrey H (2022) Neutrophil-Associated Responses to Vibrio cholerae Infection in a Natural Host Model. Infection and immunity, 90 (3). ISSN 0019-9567