Early immune and host cell responses to Cryptosporidium infection

Abstract

Cryptosporidium spp. are opportunistic protozoan parasites that infect epithelial cells of the small intestine and cause diarrheal illness in both immunocompetent and immunodeficient individuals. These infections may be more severe in immunocompromised individuals and young children, especially in children under 2 in developing countries. The parasite has a global distribution and is an important cause of childhood diarrhea where it may result in cognitive impairment and growth deficits. Current therapies are limited with nitazoxanide being the only FDA-approved drug. However, it is not efficacious in immunocompromised patients. Additionally, there are no vaccines for cryptosporidiosis available. While acquired immunity is needed to clear Cryptosporidium parasites completely, innate immunity and early responses to infection are important in keeping the infection in check so that adaptive responses have time to develop. Infection is localized to the epithelial cells of the gut. Therefore, host cell defenses are important in the early response to infection and may be triggered through toll receptors or inflammasomes which induce a number of signal pathways, interferons, cytokines, and other immune mediators. Chemokines and chemokine receptors are upregulated which recruit immune cells such neutrophils, NK cells, and macrophages to the infection site to help in host cell defense as well as dendritic cells that are an important bridge between innate and adaptive responses. This review will focus on the host cell responses and the immune responses that are important in the early stages of infection.

The role of veterinarians in zoonosis prevention: Advising families of immunocompromised children with pets

“…However, these pets are frequent Salmonella carriers, and zoonotic transmission of these bacteria has been extensively reported among owners [ 36 ], with children and immunocompromised hosts at special risk for this infection. In addition, reptiles could be Cryptosporidium carriers [ 6 ], and this pathogen is relevant for immunocompromised hosts [ 37 ]. Many veterinarians are not aware of the zoonotic risk of keeping birds in the household of immunocompromised patients.…”

Cryptosporidium parvum infection alters the intestinal mucosa transcriptome in neonatal calves: implications for immune function

“…Our knowledge of cattle chemokine families and their specificity is limited; the ones identified here were not previously reported in dairy cows with respect to C. parvum infection, and also differ from those commonly described in the other species, emphasizing the interspecies differences. As reported in the literature, during cryptosporidium infection, chemokines assist with the migration of inflammatory and adaptive immune cells such as neutrophils, NK cells, macrophages, and DCs to the infection site ( 40 , 41 ). Our bioinformatics analysis suggests the possible recruitment of granulocyte (neutrophils, eosinophils, mast cells and basophils) and mononuclear cell (lymphocytes and monocytes) recruitment during calves’ C. parvum infection, which require further validation.…”

“…The other component of adaptive immune cells consists of B cells, whose involvement in the immune response during Cryptosporidium infection is controversial. It has been reported that B cell free mice are able to remove C. parvum parasites, and that Igs do not control protozoan parasite replication ( 41 ). However, it is known that individuals with deficiencies in Igs (IgM and IgA) are more susceptible to Cryptosporidium infection ( 41 ).…”

“…It has been reported that B cell free mice are able to remove C. parvum parasites, and that Igs do not control protozoan parasite replication ( 41 ). However, it is known that individuals with deficiencies in Igs (IgM and IgA) are more susceptible to Cryptosporidium infection ( 41 ). Moreover, cytokines and chemokines produced by B cells directly affect DCs and T cells.…”

Pyroptosis Tuning in Intestinal Cryptosporidiosis via the Natural Histone Deacetylase Inhibitor Romidepsin

“…The provoked inflammatory response against cryptosporidial infection disturbs the gut homeostasis and results in pro‐inflammatory cytokine release and leukocyte infiltration [63]. Furthermore, dendritic cells produce IL‐12, which helps in macrophage and innate lymphocyte activation, and IFN‐γ generation [64].…”