|Knowles, Donald - Don|
Submitted to: Veterinary Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/27/2006
Publication Date: 5/15/2006
Citation: Brown, W.C., Norimine, J., Knowles Jr, D.P., Goff, W.L. 2006. Immune control of babesia bovis infection. Veterinary Parasitology. 138:75-87. Interpretive Summary: This review article describes recent collaborative research efforts between ARS and WSU laboratories concerned with determining the innate and acquired immunity in cattle to infection with the tick-transmitted pathogen Babesia bovis.
Technical Abstract: Babesia bovis causes an acute and often fatal infection in adult cattle, which if resolved, leads to a state of persistent infection in otherwise clinically healthy cattle. Persistently infected cattle are generally resistant to reinfection with related parasite strains, and this resistance in the face of infection is termed concomitant immunity. Young animals are generally more resistant than adults to B. bovis infection, which is dependent on the spleen. Despite the discovery of B. bovis over a century ago, there are still no safe and effective vaccines that protect cattle against this most virulent of babesial pathogens. Immunodominant antigens identified by serological reactivity and dominant T-cell antigens have failed to protect cattle against challenge. This review will describe the innate and acquired immune mechanisms that define resistance in young calves and correlate with the development of concomitant immunity in older cattle following recovery from clinical disease. The first sections will discuss the innate immune responses by peripheral blood- and spleen-derived macrophages in cattle induced by B. bovis merozoites and their products, that limit parasite replication, and comparison of natural killer cell responses in the spleens of young (resistant) and adult (susceptible). Later sections will describe a proteomic approach to discover novel antigens, especially those recognized by immune CD4+ T-lymphocytes. Because immunodominant antigens have failed to stimulate protective immunity, identification of subdominant antigens may prove to be important for effective vaccines. Identification of CD4+ T-cell immunogenic proteins and their epitopes, together with the MHC class II restricting elements, now makes possible the development of MHC class II tetramers and application of this technology to both quantify antigen-specific lymphocytes during infection and discover novel antigenic epitopes. Finally, with the imminent completion of the Babesia bovis genome-sequencing project, strategies using combined genomic and proteomic approaches to identify novel vaccine candidates will be reviewed. The availability of an annotated B. bovis genome will, for the first time, enable identification of non-immunodominant proteins that may stimulate protective immunity.