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The protozoan parasite Histomonas meleagridis is the causative agent of histomonosis in gallinaceous birds, predominantly in turkeys and chickens. Depending on the host species the outcome of the disease can be very severe with high mortality as observed in turkeys, whereas in chickens the mortality rates are generally lower. The disease is known for more than 100 years when in vitro and in vivo investigations started to understand histomonosis and the causative pathogen. For decades histomonosis could be well-controlled by effective drugs for prevention and therapy until the withdrawal of such chemicals for reasons of consumer protection in Europe, the USA and additional countries worldwide. Consequently, research efforts also focused to find new strategies against the disease, resulting in the development of an efficacious live-attenuated vaccine. In addition to efficacy and safety several studies were performed to obtain a deeper understanding of the immune response of the host against H. meleagridis. It could be demonstrated that antibodies accumulate in different parts of the intestine of chickens following infection with H. meleagridis which was much pronounced in the ceca. Furthermore, expression profiles of various cytokines revealed that chickens mounted an effective cecal innate immune response during histomonosis compared to turkeys. Studying the cellular immune response following infection and/or vaccination of host birds showed a limitation of pronounced changes of B cells and T-cell subsets in vaccinated birds in comparison to non-protected birds. Additionally, numbers of lymphocytes including cytotoxic T cells increased in the ceca of diseased turkeys compared to infected chickens suggesting an immunopathological impact on disease pathogenesis. The identification of type 1 and type 2 T-helper (Th) cells in infected and lymphoid organs by in situ hybridization did not show a clear separation of Th cells during infection but revealed a coherence of an increase of interferon (IFN)-γ mRNA positive cells in ceca and protection. The present review not only summarizes the research performed on the immune response of host birds in the course of histomonosis but also highlights the specific features of H. meleagridis as a model organism to study immunological principles of an extracellular organism in birds.

Histomonosis is a parasitic disease of gallinaceous birds characterized by necrotic lesions in cacum and liver that usually turns fatal in turkeys while it is less severe in chickens. Vaccination using in vitro attenuated Histomonas meleagridis has been experimentally shown to confer protection against histomonosis. The protective mechanisms that underpin the vaccine-induced immune response are not resolved so far. Therefore, the actual study aimed to evaluate the location and quantitative distribution patterns of signature cytokines of type 1 [interferon gamma (IFN-γ)] or type 2 [interleukin (IL)-13] immune responses in vaccinated or infected hosts. An intergroup and interspecies difference in the spatial and temporal distribution patterns of cytokine mRNA positive cells was evident. Quantification of cells showed a significantly decreased percentage of IFN-γ mRNA positive cells at 4 days post-inoculation (DPI) in caeca of turkeys inoculated exclusively with the attenuated or the virulent inocula, compared to control birds. The decrement was followed by a surge of cells expressing mRNA for IFN-γ or IL-13, reaching a peak of increment at 10 DPI. By contrast, turkeys challenged following vaccination showed a slight increment of cecal IFN-γ mRNA positive cells at 4 DPI after which positive cell counts became comparable to control birds. The increase in infected birds was accompanied by an extensive distribution of positively stained cells up to the muscularis layer of cecal tissue whereas the vaccine group maintained an intact mucosal structure. In chickens, the level of changes of positive cells was generally lower compared to turkeys. However, control chickens were found with a higher percentage of IFN-γ mRNA positive cells in cecum compared to their turkey counterparts indicating a higher resistance to histomonosis, similar to the observation in immunized turkeys. In chickens, it could be shown that the changes of cytokine-positive cells were related to variations of mononuclear cells quantified by immunofluorescence. Furthermore, gene expression measured by reverse transcription quantitative real time PCR confirmed variations in organs between the different groups of both bird species. Overall, it can be concluded that a proportionally increased, yet controlled, allocation of IFN-γ mRNA positive cells in caeca hallmarks a protective trait against histomonosis.