CYTOKINE GENE EXPRESSION DURING IN VIVO IMMUNE RESPONSE

Project Details

Description

Gastrointestinal roundworm parasites within the genera Necator,
Ancylostoma, Ascaris, Trichinella, and Strongyloides infect approximately
25% of humanity and cause considerable morbidity and mortality. Our
investigations of mice infected with an enteric roundworm parasite,
Heligmosomoides polygyrus, have revealed that specific cytokines are
responsible for the development of eosinophilia, serum IgE responses, and
mucosal mastocytosis: disease characteristics that these mice share with
roundworm-infected humans. Most importantly, the cytokine IL-4 has been
shown to be essential for immunity to a challenge infection. We have now
used a quantitative reverse transcriptase-polymerase chain reaction (RT-
PCR) technique to analyze in vivo cytokine gene expression in different
lymphoid organs of H. polygyrus-infected mice. We have documented a
vigorous cytokine response in Peyer's patch and mesenteric lymph node
cells, but not in spleen cells. IL-3, IL-4, IL-5, and IL-9 gene
expression are considerably elevated, while IL-2, IL-10, and IFN-gamma are
not. We now plan to continue these studies by addressing the following
issues: 1) Which cell types express, at both the mRNA and protein levels,
the different cytokines? 2) How does cytokine expression differ in
primary vs. challenge infections? 3) Do cytokines produced at early
stages of infection influence the response at later stages of the primary
and also in the challenge infection? 4) What cytokine responses are made
early after infection by cells immediately proximate to parasite larvae?
We believe that answers to these questions are obtainable with the RT-PCR
and ELISPOT techniques that we have developed in our laboratories and with
the in situ staining techniques that have been used by our collaborator,
Eric Claassen. The answers obtained from these studies should be useful
in the planning of therapeutic protocols to protect against, or to treat,
gastrointestinal infection.
StatusFinished
Effective start/end date8/1/946/30/15

Funding

  • National Institutes of Health: $271,398.00
  • National Institutes of Health: $349,875.00
  • National Institutes of Health: $366,215.00
  • National Institutes of Health: $390,000.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $331,745.00
  • National Institutes of Health: $263,493.00
  • National Institutes of Health: $382,239.00
  • National Institutes of Health: $255,820.00
  • National Institutes of Health: $336,825.00
  • National Institutes of Health: $341,654.00
  • National Institutes of Health: $382,239.00
  • National Institutes of Health: $168,413.00
  • National Institutes of Health: $143,285.00
  • National Institutes of Health: $386,100.00
  • National Institutes of Health
  • National Institutes of Health: $242,675.00
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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