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United States Department of Agriculture

Agricultural Research Service

Title: Il-4 and Il-10 Inhibition of Ifn-Gamma and Tnf-Alpha Dependent Nitric Oxide Production from Bovine Mononuclear Phagocytes Exposed to Babesia Bovis Merozoites

Authors
item Goff, Willard
item Johnson, W Carl
item Parish, S - WASHINGTON STATE UNIV
item Barrington, G - WASHINGTON STATE UNIV
item Elsasser, Theodore
item Davis, W - WASHINGTON STATE UNIV
item Valdez, Reginald

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 29, 2001
Publication Date: N/A

Interpretive Summary: Mononuclear phagocytes (MP) are a type of white blood cell involved in immune responses, and are the first cells that encounter foreign invading disease agents. MP are capable of producing molecules that kill microbial pathogens, including Babesia bovis, a tick-borne disease microbial agent. One of these molecules is nitric oxide. Nitric oxide is produced or inhibited in MP after interacting with other molecules called cytokines. Some cytokines induce nitric oxide and others shut the production off. In this study, we identified two cytokines that induce the production, and two that inhibit the production in MP from cattle. We determined that when MP from cattle are exposed to Babesia bovis, nitric oxide is produced only in the presence of both of the induction cytokines, and that if either of the two inhibiting cytokines are present, nitric oxide is not produced. These observations are important to the design of improved vaccines by identifying cytokines that need to be stimulated by the vaccine, or added with it to provide optimal stimulation of MP.

Technical Abstract: Bovine mononuclear phagocytes have been shown to respond to the co- stimulants, IFN-gamma plus TNF-alpha with the production of nitric oxide. Purified Babesia bovis merozoites were incapable of inducing nitric oxide production in MP without the exogenous addition of IFN- gamma and TNF-alpha unless undifferentiated monocytes taken ex vivo were producing TNF-alpha endogenously. Under the latter condition, the nitric oxide production resulting from merozoite stimulation remained IFN-gamma-dependent. Both IL-4 and IL-10 inhibited iNOS expression and nitric oxide production. Merozoites were capable of inducing both IL-12 and TNF-alpha mRNA from monocyte-derived macrophages. Together, these results suggest that the immune response to B. bovis infection has type-1 characteristics.

Last Modified: 11/28/2014
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