Suppressed T helper 2 immunity and prolonged survival of a nematode parasite in protein-malnourished mice.
Protein malnutrition may increase susceptibility to gastrointestinal parasitic infections, possibly as a result of impaired intestinal and/or systemic T helper 2 (Th2) effector responses induced by down-regulation of Th2 cytokines and/or up-regulation of Th1 cytokines. To test this hypothesis, female BALB/c mice (n = 18/diet) were fed a control (24%), marginal (7%), or deficient (3%) protein diet and given a challenge infection with Heligmosomoides polygyrus. The 3% mice had higher worm burdens at 1, 2, and 4 weeks postchallenge infection (pci), lower increases in serum IgE, reduced intestinal eosinophilia, and depressed mucosal mast cell proliferation and activation at 1-2 weeks pci. To determine whether these suppressed effector responses resulted from altered spleen and mesenteric lymph node (MLN) cytokine production, cells were restimulated in vitro with parasite antigen and cytokine concentrations were measured. Deficient MLN cells secreted significantly less IL-4 and more IFN-gamma at 1-2 weeks pci than did control MLN cells. Deficient spleen cells also secreted more IFN-gamma at 2 weeks pci compared with control spleen cells. From reverse transcription-PCR analyses, the 3% mice also had lower IL-4 mRNA level in spleen and MLN at 1-2 weeks pci. Our study supports the hypothesis that protein malnutrition increases the survival of a nematode parasite by decreasing gut-associated IL-4 (Th2) and increasing IFN-gamma (Th1) within 2 weeks pci, leading to reduced intestinal and systemic Th2 effector responses.
Ing
R
R
Institute of Parasitology and School of Dietetics and Human Nutrition, McGill University (Macdonald Campus), 21,111 Lakeshore Road, Ste-Anne de Bellevue, Quebec H9X 3V9, Canada.
Su
Z
Z
Scott
M E
ME
Koski
K G
KG
D000818:Animals; D004044:Dietary Proteins / Q000009:adverse effects* / Q000378:metabolism; D005260:Female; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009351:Nematospiroides dubius; D009748:Nutrition Disorders / Q000150:complications / Q000276:immunology / Q000378:metabolism; D017206:Strongylida Infections / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*
D004044:Dietary Proteins