Expression of IL-10 and TGF-ß1 in horses experimentally infected with T. equi merozoites can be linked to antibody production but not modulation of pro-inflammatory responses

Authors: ONZERE, CYNTHIA - Washington State University; Bastos, Reginaldo; BISHOP, RICHARD - Washington State University; Suarez, Carlos; FRY, LINDSAY - Former ARS Employee

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/23/2024
Publication Date: 5/12/2024
Citation: Onzere, C.K., Bastos, R.G., Bishop, R.P., Suarez, C.E., Fry, L.M. 2024. Expression of IL-10 and TGF-ß1 in horses experimentally infected with T. equi merozoites can be linked to antibody production but not modulation of pro-inflammatory responses. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2024.1370255.
DOI: https://doi.org/10.3389/fimmu.2024.1370255

Interpretive Summary: T. equi) is a parasite that replicates in blood and causes severe anemia in equids. Significant knowledge gaps in our understanding the of host-parasite relationship imped the development of effective vaccines to control T. equi. The objective of this study was to evaluate the T. equi-horse interactions following primary and secondary parasite exposure. We assessed the horse immune response and its association with clinical disease. The results showed low and inconsistent expression of pro-inflammatory cytokines during both primary and secondary exposure, indicating no correlation between the symptoms observed during infection and expression of the cytokines. Interestingly, we observed high expression of IL-10 and TGF-ß, two critical anti-inflammatory cytokines, which were linked to antibody production in infected horses. Collectively, data suggest that the symptoms T. equi infection are not due to the undesirable effects of pro-inflammatory responses, but likely associated with the lysis of red blood cells during parasite replication in the host blood. Future work should focus on a more in-depth analysis of additional host and parasite mechanisms that may be exploited to control T. equi.

Technical Abstract: Theileria equi (T. equi) is an apicomplexan parasite that causes severe hemolytic anemia in equids. Presently, there is inadequate knowledge of the immune responses induced by T. equi in equid hosts impeding understanding of the host parasite relationship and development of potent vaccines for control of T. equi infection. The objective of this study was to evaluate the host-parasite dynamics between T. equi merozoites and infected horses by assessing cytokine expression during primary and secondary parasite exposure, and to determine whether the pattern of expression correlated with clinical indicators of disease. Our findings showed that the expression of pro-inflammatory cytokines was very low and inconsistent during both primary and secondary infection. There was also no correlation between the symptoms observed during primary infection and expression of the cytokines. This suggests that the symptoms might have occurred primarily due to hemolysis and likely not the undesirable effects of pro-inflammatory responses. However, IL-10 and TGF-ß1 were highly expressed in both phases of infection, and their expression was linked to antibody production but not moderation of pro-inflammatory cytokine responses.