A potential role for interleukin-18 in inhibition of the development of Cryptosporidium parvum.
Accumulating evidence suggests that intestinal epithelial cells (IECs) constitutively express the immunoregulatory cytokine interleukin (IL)-18. IECs also serve as the host cell for the intracellular parasitic protozoan Cryptosporidium parvum. In the present study, C. parvum infection of a human enterocyte cell-line HCT-8 resulted in increased expression of IL-18 mRNA as measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR). IL-18 protein was detected in control uninfected cells and following infection there was increased expression as measured by enzyme-linked immunosorbent assay (ELISA). Gene expression revealed the presence of the IL-18 receptor subunits not only in cell-lines but also in freshly isolated IECs, suggesting that IL-18-mediated signalling events may contribute to epithelial host defence during infection. Recombinant IL-18 inhibited intracellular development of the parasite in HCT-8 and HT-29 cells. Increased expression of bactericidal antibiotic peptides LL-37 and alpha-defensin 2 by IL-18 in HCT-8 and HT-29 cells may represent one mode of action by which this pluripotent cytokine aids in limiting the development of intracellular pathogens such as C. parvum in the gastrointestinal tract.
McDonald
V
V
Barts and the London School of Medicine and Dentistry, Institute of Cell and Molecular Science, Centre for Gastroenterology, London, UK.
Pollok
R C G
RC
Dhaliwal
W
W
Naik
S
S
Farthing
M J G
MJ
Bajaj-Elliott
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D003457:Cryptosporidiosis / Q000276:immunology* / Q000378:metabolism; D016785:Cryptosporidium parvum / Q000187:drug effects / Q000502:physiology*; D020895:Enterocytes / Q000276:immunology* / Q000382:microbiology*; D019073:HT29 Cells; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics / Q000502:physiology*; D053727:Interleukin-18 Receptor alpha Subunit; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000378:metabolism; D053724:Receptors, Interleukin-18; D011994:Recombinant Proteins / Q000494:pharmacology; D023084:alpha-Defensins / Q000378:metabolism; D054804:Cathelicidins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D011994:Recombinant Proteins; D023084:alpha-Defensins; D054804:Cathelicidins