Expression of IL-15 and IL-4 in IFN-gamma-independent control of experimental human Cryptosporidium parvum infection.
We have previously demonstrated interferon gamma (IFN-gamma) in intestinal mucosa after experimental human Cryptosporidium parvum infection, but expression was limited to sensitized volunteers. To characterize IFN-gamma-independent mechanisms in control of infection, jejunal biopsies from immunocompetent volunteers experimentally challenged with C. parvum were examined by in situ hybridization for interleukin (IL-)15 and IL-4 mRNA with confirmation by immunohistochemistry. Cytokine expression was correlated with prechallenge anti- C. parvum IgG, symptoms, oocyst shedding, and prior IFN-gamma expression data. IL-15 expression was noted only in those without prior sensitization, who did not express IFN-gamma. By contrast, expression of IL-4 was associated with prior sensitization. IL-15 was only detected in those with symptoms (6/14 symptomatic vs 0/3 asymptomatic, P<0.05). Among 14 volunteers who did not express IFN-gamma, oocyst shedding was lower in those expressing IL-15. Overall, 14/15 volunteers who did not shed oocysts expressed either IFN-gamma or IL-15. There was no correlation between expression of IL-4 and symptoms or oocyst shedding. In conclusion, IL-15 expression was associated with control of oocyst shedding in those not expressing IFN-gamma. These data suggest that IL-15 is involved in IFN-gamma independent mechanisms of control of human cryptosporidiosis, perhaps via activation of the innate immune response.
Robinson
P
P
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Okhuysen
P C
PC
Chappell
C L
CL
Lewis
D E
DE
Shahab
I
I
Lahoti
S
S
White
A C
AC
D000293:Adolescent; D000328:Adult; D000818:Animals; D001706:Biopsy; D003457:Cryptosporidiosis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D016785:Cryptosporidium parvum / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D005753:Gastric Mucosa / Q000382:microbiology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000096:biosynthesis*; D019409:Interleukin-15 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism / Q000382:microbiology; D008875:Middle Aged; D010957:Plasmids / Q000378:metabolism; D013997:Time Factors
D018076:DNA, Complementary; D007074:Immunoglobulin G; D019409:Interleukin-15; D015847:Interleukin-4; D007371:Interferon-gamma