T helper cell type 2 responsiveness predicts future susceptibility to gastrointestinal nematodes in humans.

Some humans are persistently more susceptible to gastrointestinal nematodes than others. Here, for the first time, susceptibility to reinfection has been linked to host cytokine responses. Ascaris lumbricoides and Trichuris trichiura abundance was assessed immediately before and 8-9 months after deworming in a Cameroonian population (starting n=191). Profiles of whole-blood cytokine responses to parasite antigens (for interleukin [IL]-5, IL-13, IL-10, IL-12p40, tumor necrosis factor- alpha , and interferon- gamma), assayed before treatment, were significantly related both to an overall measure of host susceptibility and to susceptibility to reinfection. Significant effects were primarily due to a negative association between IL-13 and IL-5 responses and infection. Persistently susceptible individuals were, therefore, characterized by a weak T helper cell type 2 response. The apparent plasticity of age-specific cytokine response-worm abundance relationships between different populations is also discussed.

[1]  R. Reyment,et al.  Multivariate Morphometrics, 2nd Edition. , 1985 .

[2]  M. Boussinesq,et al.  Th2 cytokines are associated with reduced worm burdens in a human intestinal helminth infection. , 2003, The Journal of infectious diseases.

[3]  R. Locksley,et al.  Coordinate Regulation of the IL-4, IL-13, and IL-5 Cytokine Cluster in Th2 Clones Revealed by Allelic Expression Patterns1 , 2000, The Journal of Immunology.

[4]  T. Nutman,et al.  Human infection with Ascaris lumbricoides is associated with a polarized cytokine response. , 2000, The Journal of infectious diseases.

[5]  T. Wynn IL-13 effector functions. , 2003, Annual review of immunology.

[6]  K. Else,et al.  The effect of challenge and trickle Trichuris muris infections on the polarisation of the immune response. , 2001, International journal for parasitology.

[7]  B. Petros,et al.  Effect of deworming on human T cell responses to mycobacterial antigens in helminth‐exposed individuals before and after bacille Calmette–Guérin (BCG) vaccination , 2001, Clinical and experimental immunology.

[8]  R. Grencis,et al.  Cytokine regulation of resistance and susceptibility to intestinal nematode infection - from host to parasite. , 2001, Veterinary parasitology.

[9]  J. Sinacore Multiple regression: Testing and interpreting interactions , 1993 .

[10]  M. Levine,et al.  Human Infection with Ascaris lumbricoides Is Associated with Suppression of the Interleukin-2 Response to Recombinant Cholera Toxin B Subunit following Vaccination with the Live Oral Cholera Vaccine CVD 103-HgR , 2001, Infection and Immunity.

[11]  L. Stephenson Pathophysiology of Intestinal Nematodes , 2002 .

[12]  J. Seed,et al.  World class parasites , 2001 .

[13]  P Garner,et al.  Effects of treatment for intestinal helminth infection on growth and cognitive performance in children: systematic review of randomised trials , 2000, BMJ : British Medical Journal.

[14]  A. Baddeley,et al.  Heavy schistosomiasis associated with poor short‐term memory and slower reaction times in Tanzanian schoolchildren , 2002, Tropical medicine & international health : TM & IH.

[15]  J. Roberts,et al.  Assessment of combined ivermectin and albendazole for treatment of intestinal helminth and Wuchereria bancrofti infections in Haitian schoolchildren. , 1999, The American journal of tropical medicine and hygiene.

[16]  M. Boussinesq,et al.  A comparison of cellular and humoral immune responses to trichuroid derived antigens in human trichuriasis , 2002, Parasite immunology.

[17]  D. Dunne,et al.  Associations between helminth infection and CD4+ T cell count, viral load and cytokine responses in HIV-1-infected Ugandan adults. , 2003, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[18]  C. Holland,et al.  The Geohelminths: Ascaris, Trichuris and Hookworm , 2010, World Class Parasites.

[19]  R. Grencis Th2-mediated host protective immunity to intestinal nematode infections. , 1997, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[20]  R. Newcombe Two-sided confidence intervals for the single proportion: comparison of seven methods. , 1998, Statistics in medicine.

[21]  D. F. Morrison,et al.  Multivariate Statistical Methods , 1968 .

[22]  A. Hall,et al.  Evidence for an association between hookworm infection and cognitive function in Indonesian school children , 1999, Tropical medicine & international health : TM & IH.

[23]  A. Hall,et al.  Antibody isotype responses to antigens of Ascaris lumbricoides in a case-control study of persistently heavily infected Bangladeshi children , 1995, Parasitology.

[24]  C. Holland,et al.  Distributions and Predisposition: People and Pigs , 2002 .

[25]  Elson,et al.  Onchocerciasis modulates the immune response to mycobacterial antigens , 1999, Clinical and experimental immunology.

[26]  Z. Bentwich,et al.  Helminths, human immunodeficiency virus and tuberculosis. , 2001, Scandinavian journal of infectious diseases.

[27]  R. Grencis,et al.  Mast cells disrupt epithelial barrier function during enteric nematode infection , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Rick M. Maizels,et al.  Immune Regulation by helminth parasites: cellular and molecular mechanisms , 2003, Nature Reviews Immunology.

[29]  M. Boussinesq,et al.  Age- and infection intensity-dependent cytokine and antibody production in human trichuriasis: the importance of IgE. , 2002, The Journal of infectious diseases.

[30]  W. Gause,et al.  The immune response to parasitic helminths: insights from murine models. , 2003, Trends in immunology.

[31]  Mathieu Nacher,et al.  Helminth infections are associated with protection from malaria-related acute renal failure and jaundice in Thailand. , 2001, The American journal of tropical medicine and hygiene.

[32]  Z. Bentwich,et al.  Geohelminths, HIV/AIDS and TB , 2002 .