Impaired basophil induction leads to an age-dependent innate defect in type 2 immunity during helminth infection in mice

J Immunol. 2011 Apr 15;186(8):4631-9. doi: 10.4049/jimmunol.1002995. Epub 2011 Mar 11.

Abstract

Parasitic-infection studies on rhesus macaque monkeys have shown juvenile animals to be more susceptible to infection than adults, but the immunological mechanism for this is not known. In this study, we investigated the age-dependent genesis of helminth-induced type 2 immune responses using adult (6-8-wk-old) and juvenile (21-28-d-old) mice. Following infection with the parasitic nematode Nippostrongylus brasiliensis, juvenile mice had increased susceptibility to infection relative to adult mice. Juvenile mice developed a delayed type 2 immune response with decreased Th2 cytokine production, IgE Ab responses, mouse mast cell protease 1 levels, and intestinal goblet cell induction. This innate immune defect in juvenile mice was independent of TLR signaling, dendritic cells, or CD4(+) cell function. Using IL-4-eGFP mice, it was demonstrated that the numbers of IL-4-producing basophil and eosinophils were comparable in young and adult naive mice; however, following helminth infection, the early induction of these cells was impaired in juvenile mice relative to older animals. In nonhelminth models, there was an innate in vivo defect in activation of basophils, but not eosinophils, in juvenile mice compared with adult animals. The specific role for basophils in this innate defect in helminth-induced type 2 immunity was confirmed by the capacity of adoptively transferred adult-derived basophils, but not eosinophils, to restore the ability of juvenile mice to expel N. brasiliensis. The defect in juvenile mice with regard to helminth-induced innate basophil-mediated type 2 response is relevant to allergic conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Basophils / immunology*
  • Basophils / metabolism
  • Disease Susceptibility / immunology
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Female
  • Flow Cytometry
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Host-Parasite Interactions / immunology
  • Immunity, Innate / immunology*
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / immunology
  • Intestines / parasitology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nippostrongylus / immunology*
  • Nippostrongylus / physiology
  • Strongylida Infections / immunology*
  • Strongylida Infections / parasitology
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism

Substances

  • Interleukin-17
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Transforming Growth Factor beta
  • Green Fluorescent Proteins
  • Interleukin-4
  • Interferon-gamma