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Heartworm disease caused by Dirofilaria immitis affects canine and feline hosts, with infections occasionally being reported in humans. Studies have shown that both dirofilarial antigens and those derived from its bacterial endosymbiont Wolbachia, interact with the host organism during canine, feline and human infections and participate in the development of the pathology and in the regulation of the host’s immune response. Both innate and acquired immune responses are observed and the development of the acquired response may depend on the host and, or on its parasitological status. This review aims at illustrating current research on the role of both D. immitis and Wolbachia, in the immunology and immunopathology of dirofilariosis.