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Title: Localized complement activation in the development of protective immunity against Ostertagia ostertagi infections in cattle

Author
item Li, Robert
item HOU, YALI - University Of Maryland
item Li, Congjun - Cj
item GASBARRE, LOUIS - Retired ARS Employee

Submitted to: Veterinary Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/10/2010
Publication Date: 10/10/2010
Citation: Li, R.W., Hou, Y., Li, C., Gasbarre, L.C. 2010. Localized complement activation in the development of protective immunity against Ostertagia ostertagi infections in cattle. Veterinary Parasitology. 174(3-4):247-256.

Interpretive Summary: Internal parasites, especially gastrointestinal nematodes, have been ranked among the top three diseases or conditions that may have a significant economic impact on the American cattle industry with an estimated annual cost in excess of $2 billion. Protective immunity to Ostertagia ostertagi infections develops very slowly and resistance to reinfection manifests only after a prolonged period of exposure. Limited knowledge in our understanding of host-parasite relationship and protective immune responses has hindered the development of vaccines and immune-modulators. In this study, we conducted a transcriptomic analysis of bovine abomasal mucosa during infection. Our data suggested enhanced tissue repair and mucin secretion in immune animals may contribute to protective immunity. We presented evidence that local complement activation may be involved in the development of long term protective immunity. Our results provided a molecular roadmap for future studies in defining host immune responses.

Technical Abstract: The gastrointestinal nematode Ostertagia ostertagi is one of major causal agents that contribute to production inefficiencies, such as reduced weight gain and milk yield, in cattle industry in the temperate region of the world. Protective immunity to infections develops very slowly and resistance to reinfection manifests only after a prolonged period of exposure. Mechanisms underlying the development of protective immunity remain largely unexplored. Immune animals, which have significantly reduced worm burdens, were developed after multiple drug-attenuated experimental infections and were compared to a primary infected group and their respective uninfected controls. In this study, transcriptomic analysis identified 3 signaling pathways, the complement system, leukocyte extravasation and acute phase responses, significantly impacted during both primary and repeat infections. The markedly increased mRNA levels of complement components C3, factor B (CFB) and factor I (CFI) in the abomasal mucosa of the infected cattle were confirmed using quantitative PCR while Western blot analysis established the presence of elevated levels of activated C3 proteins in the mucosa. One of the initiators of local complement activation could be related to secretory IgA and IgM because infections significantly upregulated expression of J chain (IGJ) as well as polymeric Ig receptor (PIGR) and an IgM-specific receptor (FAIM3), suggesting sustained increase in both synthesis and transepithelial transport of IgA and IgM during the infection. The elevated levels of pro-inflammatory cytokines, such as IL-4 and IL-1ß, during infection may be involved in gene regulation of complement components. Our data suggested enhanced tissue repair and mucin secretion in immune animals may also contribute to protective immunity. Our results presented the first piece of evidence that local complement activation may be involved in the development of long term protective immunity and provided a novel mechanistic insight into resistance against Ostertagia ostertagi in cattle.