Gr-1+ cells and the response to nematode parasites

Project Details

Description

T helper 2 (Th2)effector cells, through Th2 cytokine production, can mediate resistance to helminthic
parasite infection. Understanding the cell and molecular interactions that lead to their differentiation is
therefore important for the development of therapies and vaccines that promote host protective immune
responses. We have begun to examine the innate response that initially develops following infection of mice
with nematode parasites to identify cell populations or signals that may be important in promoting adaptive
immunity that leads to the developing of IL-4producing Th2 cells. Global gene expression analyses of
draining lymph nodes shortly after parasite infection showed pronounced increases in chemokines, including
MCP-1 and CXCR3 ligands. Both chemokines are kn ow to recruit monocytes and granulocytes. Gr-1 is a
cell surface marker shared by these cell populations and also plasmacytoid dendritic cells. Draining lymph
nodes showed pronounced increases in Gr-1+ cells at 4 and 16 hours after inoculation with the intestinal
nematode parasite, N. brasiliensis. Treatment with anti-GR-1 antibody caused marked increases in lymph
node IFN-v expression at 18 hours after N. brasiliensis inoculation and decreased IL-4 expression and host
resistance was observed at 7 days after inoculation. In the proposed studies, we will examine the function of
Gr-1+ cells in promoting the development of Th2 effector cells in vivo. Specifically, we propose to identify
the chemokine/chemokine receptors that mediate the recruitment of Gr-1+ cells to the peripheral lymph
nodes at early stages of the immune response to N. brasiliensis. We will also elucidate the mechanism of
how Gr-1+ cells suppress IFN-y elevations and promote Th2 cell development leading to host resistance by
examining Gr-1+ cell interactions with developing Th2 cells in situ. Finally, we will address in two parasite
models, N. brasiliensis and H. polygyrus, the role of Gr-1+ cells in the development of the host protective
primary and memory response.
StatusFinished
Effective start/end date3/15/062/29/12

Funding

  • National Institute of Allergy and Infectious Diseases: $370,305.00
  • National Institute of Allergy and Infectious Diseases: $370,305.00
  • National Institute of Allergy and Infectious Diseases: $377,476.00
  • National Institute of Allergy and Infectious Diseases: $366,602.00

ASJC

  • Cell Biology
  • Parasitology
  • Immunology

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