Katherine A. Taylor

Immune responses of cattle to African trypanosomes: protective or pathogenic?

Trypanosomosis in domestic livestock negatively impacts food production and economic growth in many parts of the world, particularly in sub-Saharan Africa. Current methods of control are inadequate to prevent the enormous annual socio-economic losses resulting from this disease. Hope for a vaccine based on the variant surface glycoprotein coat was abandoned several years ago when the complexity of the parasites antigenic repertoire was appreciated. As a result, research is now focused on identifying invariant trypanosome components as potential targets for interrupting infection or infection-mediated disease. The identification of immune mechanisms involved in parasite and disease control, or conversely those responses that are associated with a poor clinical outcome, should facilitate the search for vaccine candidates and subsequent vaccine design strategies. To this end, comparative studies on the immune responses of trypanotolerant and trypanosusceptible breeds of cattle can be exploited. These studies have revealed that trypanotolerant and trypanosusceptible breeds of cattle have distinct antibody responses. Trypanosusceptible cattle produce high titres of polyspecific IgM but fail to produce IgG to specific trypanosome antigens. In contrast, although T cell and macrophage/monocyte responses of infected cattle are depressed, significant differences have not been described between tolerant and susceptible breeds of cattle. In this review, isotype-dependent effector mechanisms, such as complement activation, binding to Fc receptors, activation of phagocytic cells, neutralisation of parasite components, clearance of immune complexes and autoimmune responses, are discussed in the context of their potential impact on either susceptibility or tolerance of cattle to trypanosomosis. In addition, the links between specific cytokine patterns, macrophage/monocyte activation and depressed T cell responses that occur during trypanosome infection are presented. The identification of mechanisms that mediate depressed immune responses might suggest novel disease intervention strategies.

Immune Response of Cattle Infected with African Trypanosomes

Trypanosomosis is the most economically important disease constraint to livestock productivity in sub-Saharan Africa and has significant negative impact in other parts of the world. Livestock are an integral component of farming systems and thus contribute significantly to food and economic security in developing countries. Current methods of control for trypanosomosis are inadequate to prevent the enormous socioeconomic losses resulting from this disease. A vaccine has been viewed as the most desirable control option. However, the complexity of the parasites antigenic repertoire made development of a vaccine based on the variable surface glycoprotein coat unlikely. As a result, research is now focused on identifying invariant trypanosome components as potential targets for interrupting infection or infection-mediated disease. Immunosuppression appears to be a nearly universal feature of infection with African trypanosomes and thus may represent an essential element of the host-parasite relationship, possibly by reducing the hosts ability to mount a protective immune response. Antibody, T cell and macrophage/monocyte responses of infected cattle are depressed in both trypanosusceptible and trypanotolerant breeds of cattle. This review describes the specific T cell and monocyte/macrophage functions that are altered in trypanosome-infected cattle and compares these disorders with those that have been described in the murine model of trypanosomosis. The identification of parasite factors that induce immunosuppression and the mechanisms that mediate depressed immune responses might suggest novel disease intervention strategies.

Enhancing effects of anti-CD40 treatment on the immune response of SCID-bovine mice to Trypanosoma congolense infection

African trypansosomes are tsetse‐transmitted parasites of chief importance in causing disease in livestock in regions of sub‐Saharan Africa. Previous studies have demonstrated that certain breeds of cattle are relatively resistant to infection with trypanosomes, and others are more susceptible. Because of its extracellular location, the humoral branch of the immune system dominates the response againstTrypanosoma congolense. In the following study, we describe the humoral immune response generated against T. congolense in SCID mice reconstituted with a bovine immune system (SCID‐bo). SCID‐bo mice infected with T. congolense were treated with an agonistic anti‐CD40 antibody and monitored for the development of parasitemia and survival. Anti‐CD40 antibody administration resulted in enhanced survival compared with mice receiving the isotype control. In addition, we demonstrate that the majority of bovine IgM+ B cells in SCID‐bo mice expresses CD5, consistent with a neonatal phenotype. It is interesting that the percentage of bovine CD5+ B cells in the peripheral blood of infected SCID‐bo mice was increased following anti‐CD40 treatment. Immunohistochemical staining also indicated increased numbers of Ig+ cells in the spleens of anti‐CD40‐treated mice. Consistent with previous studies demonstrating high IL‐10 production during high parasitemia levels in mice and cattle, abundant IL‐10 mRNA message was detected in the spleens and peripheral blood of T. congolense‐infected SCID‐bo mice during periods of high parasitemia. In addition, although detected in plasma when parasites were absent or low in number, bovine antibody was undetectable during high parasitemia. However, Berenil treatment allowed for the detection of VSG‐specific IgG 14 days postinfection in T. congolense‐infected SCID‐bo mice. Overall, the data indicate that survival of trypanosome‐infected SCID‐bo mice is prolonged when an agonistic antibody against bovine CD40 (ILA156) is administered. Thus, stimulation of B cells and/or other cell types through CD40 afforded SCID‐bo mice a slight degree of protection during T. congolense infection.

In vitro activation and detection of antibody-secreting cells from Trypanosoma congolense-infected cattle

B cells from the peripheral blood and spleen of Trypanosoma congolense-infected cattle and from the peripheral blood of an uninfected cohort were analysed for ability to secrete antibody and for expression of surface antigens before and after in vitro culture with interleukin-2, lipopolysaccharide and pokeweed mitogen. Antibody-secreting cells (ASC) were only detected in lymphocytes from peripheral blood after in vitro stimulation. The frequency of ASC was greater in cultures of lymphocytes from infected cattle than from the uninfected cohort. The frequency of ASC was positively correlated with the number of B cells expressing the transferring receptor but not with the expression of the CD5 antigen.