Associations between mucosal innate and adaptive immune responses and resolution of diarrheal pathogen infections.
The identification of immune response mechanisms that contribute to the control of diarrheal disease in developing countries remains an important priority. We addressed the role of fecal chemokines and cytokines in the resolution of diarrheal Escherichia coli and Giardia lamblia infections. Stools collected from 127 Mexican children 5 to 15 months of age enrolled in a randomized, double-blind, placebo-controlled, vitamin A supplementation trial were screened for enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC), and Giardia lamblia. Fecal concentrations of tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), interleukin-4 (IL-4), IL-5, IL-6, IL-8, IL-10, and interferon-gamma (IFN-gamma) were determined. Hazard models incorporating cytokine variables were fit to durations of asymptomatic and symptomatic pathogen infections, controlling for treatment group. Increased levels of TNF-alpha and IL-6 were associated with decreased durations of EPEC infection and increased ETEC durations. Increased IL-4 and IFN-gamma levels were associated with decreased and increased durations, respectively, of both EPEC and ETEC infections. Increased IL-10 levels were associated with increased and decreased durations of asymptomatic and symptomatic EPEC infections, respectively, and increased durations of both asymptomatic and symptomatic ETEC infections. Increased levels of MCP-1, IFN-gamma, IL-4, and IL-5 were associated with increased G. lamblia infection duration, while increased IL-8 levels were associated with decreased durations. Differences in proinflammatory and Treg cytokine levels are associated with differences in the resolution of inflammatory and noninflammatory pathogen infections.
Long
Kurt Z
KZ
Nutrition Environmental Health and Disease and Injury Control Unit, The University of Queensland, School of Population Health, Herston Rd., Herston, Queensland 4006, Australia. k.long@uq.edu.au
Rosado
Jorge L
JL
Santos
José Ignacio
JI
Haas
Meredith
M
Al Mamun
Abdullah
A
DuPont
Herbert L
HL
Nanthakumar
Nanda N
NN
Estrada-Garcia
Teresa
T
D056704:Adaptive Immunity; D000818:Animals; D016207:Cytokines / Q000032:analysis; D003967:Diarrhea / Q000276:immunology*; D004751:Enteritis / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology*; D005243:Feces / Q000737:chemistry; D016829:Giardia lamblia / Q000276:immunology*; D005873:Giardiasis / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007223:Infant; D008800:Mexico; D016032:Randomized Controlled Trials as Topic; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014801:Vitamin A / Q000008:administration & dosage
D016207:Cytokines; D014801:Vitamin A