Immunity and resistance to cryptosporidiosis: the intricate ways of an enigmatic parasitosis

Abstract

Genus Cryptosporidium includes around 30 known apicomplexan parasitic species which infect the gastrointestinal tract and rarely the respiratory system of more than 300 vertebrate animals. The immune response against infection by Cryptosporidium spp. includes all strata of innate and adaptive immunity with differences in their significance. The mucosal immunity, expressed predominantly by the “sentinel” role of epitheliocytes, is fundamental to the resistance against an infection (mainly via activation of the TLR4/NF-κB signalling axis). The vast array of epithelial chemokines and cytokines initiate the local inflammatory processes, attract effector cells and may directly suppress the parasite adhesion. The second line of defence includes IFN-γ-production by the NK cells in combination with their innate cytotoxicity against the parasite and the infected epitheliocytes. The adaptive immunity against the parasite depends predominantly on cytotoxic CD4+ Th1-lymphocytes, which makes IFN-γ central to the acquired response too. CD8+ cells aid to some extent the activity of Th1-cells but their involvement is not decisive. While Cryptosporidium infection elicits the synthesis of specific serum and mucosal antibodies, the humoral immunity is of minor importance. In immunocompromised hosts, infants and malnourished children, the mild and usually self-limiting infection can become life-threatening or take a chronic course. It is the second leading cause of fatal diarrhoea in children and one of the major opportunistic pathogens in the continually expanding group of patients with immunodeficiencies and systemic chronic diseases. Unravelling the mechanisms of resistance against Cryptosporidium infection is fundamental for the successful prevention of the disease.