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Secreted proteins are reported to induce cell-mediated immunity characterised by the production of interferon-gamma (IFN)-γ. In this study three open reading frames (ORFs) (Erum8060, Erum7760, Erum5000) encoding secreted proteins were selected from the Ehrlichia ruminantium (Welgevonden) genome sequence using bioinformatics tools to determine whether they induce a cellular immune response in vitro with mononuclear cells from needle and tick infected animals. The whole recombinant protein of the three ORFs as well as four adjacent fragments of the Erum5000 protein (Erum5000A, Erum5000B, Erum5000C, Erum5000D) were successfully expressed in a bacterial expression system which was confirmed by immunoblots using anti-His antibodies and sheep sera. These recombinant proteins were assayed with immune sheep and cattle peripheral blood mononuclear cells (PBMCs), spleen and lymph node (LN) cells to determine whether they induce recall cellular immune responses in vitro. Significant proliferative responses and IFN-γ production were evident for all recombinant proteins, especially Erum5000A, in both ruminant species tested. Thus overlapping peptides spanning Erum5000A were synthesised and peptides that induce proliferation of memory CD4+ and CD8+ T cells and production of IFN-γ were identified. These results illustrate that a Th1 type immune response was elicited and these recombinant proteins and peptides may therefore be promising candidates for development of a heartwater vaccine.

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Animal and human studies have demonstrated that helminth infections are associated with a decreased prevalence of type 2 diabetes mellitus (T2DM). Lack of exposure to helminth infections has been postulated to be one mechanism to explain the markedly increased prevalence of T2DM in developed countries. However, there is still paucity of information regarding the immunological interactions between helminth infections and T2DM. The study aimed at reviewing peer-reviewed articles on host immune and pathophysiological outcomes from human and laboratory animal studies of helminth infections and T2DM comorbidity. A literature search was carried out in Google Scholar, PubMed, and EBSCOhost databases using the following keywords; immune responses OR immune modulation of helminth infections OR parasites infections AND Type 2 diabetes comorbidity in humans AND experimental/laboratory animals. Results showed that helminth infections provided some degree of protection from the pathology associated with T2DM by modulating the surrounding cytokine and chemokine milieu in humans and animals. Whilst there is some evidence regarding the protective effects of helminth infections to T2DM in cases of comorbidity, there is paucity of research in both laboratory animals and humans, with reference to the immunological and pathophysiological mechanisms which occur during comorbidity, and these constitute gaps for future research.

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Diabetes mellitus is a chronic metabolic disease induced by the inability to control high blood glucose level. Helminth-induced immunomodulation has been reported to prevent or delay the onset of type 2 diabetes mellitus (T2DM), which, in turn, ameliorates insulin sensitivity. Therefore, there is a need to understand the underlying mechanisms utilized by helminths in metabolism and the induction of immuno-inflammatory responses during helminthic infection and T2DM comorbidity. This study aimed at using a laboratory animal model to determine the cytokines, chemokines and haematological indices in diabetic (T2DM) male Sprague Dawley (SD) rats infected with Trichinella zimbabwensis. One hundred and two male SD rats (160–180 g) were randomly selected into three experimental groups (i. T2DM-induced group (D) ii. T. zimbabwensis infected + T2DM group (TzD) and iii. T. zimbabwensis-infected group (Tz)). Rats selected for the D group and TzD group were injected with 40 mg/kg live weight of streptozotocin (STZ) intraperitoneally to induce T2DM, while animals in the Tz and TzD group were infected with T. zimbabwensis. Results showed that adult T. zimbabwensis worm loads and mean T. zimbabwensis larvae per gram (lpg) of rat muscle were significantly higher (p < 0.001) in the Tz group when compared to the TzD group. Blood glucose levels in the D group were significantly higher (p < 0.001) compared to the TzD group. An increase in insulin concentration was observed among the TzD group when compared to the D group. Liver and muscle glycogen decreased in the D when compared to the TzD group. A significant increase (p < 0.05) in red blood cells (RBCs) was observed in the D group when compared to the TzD and Tz groups. An increase in haematocrit, haemoglobin, white blood cells (WBCs), platelet, neutrophils and monocyte were observed in the D group when compared to the TzD group. TNF-α, IFN-γ, IL-4, IL-10 and IL-13 concentrations were elevated in the TzD group when compared to the D and Tz groups, while IL-6 concentration showed a significant reduction in the Tz when compared to the D and the TzD groups. A significant increase in CCL5 in the D and TzD groups was observed in comparison to the Tz group. CXCL10 and CCL11 concentration also showed an increase in the TzD group in comparison to the Tz and the D groups. Overall, our results confirm that T. zimbabwensis, a parasite which produces tissue-dwelling larvae in the host, regulates T2DM driven inflammation to mediate a positive protective effect against T2DM outcomes.