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Pulmonary Division, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109; and
Department of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712
Pulmonary clearance of the encapsulated yeast Cryptococcus
neoformans requires the development of T1-type immunity. The
objective of this study was to determine the role of CCR2 in leukocyte
recruitment and development of T1-type cell-mediated immunity during
pulmonary C. neoformans infection. Intratracheal
inoculation of C. neoformans into CCR2 knockout
(CCR2-/-) mice produced a prolonged pulmonary infection
(5000-fold CFU at 6 wk compared with CCR2+/+ mice) and
significant dissemination to the spleen and brain (160- and 800-fold
greater). In addition, CCR2 deficiency resulted in significantly
reduced recruitment of macrophages (weeks 13) and CD8+ T
cells (weeks 12) into the lungs. The immune response in
CCR2-/- mice was characterized by chronic pulmonary
eosinophilia, crystal deposition in the lungs, pulmonary leukocyte
production of IL-4 and IL-5 but not IFN-
, lack of anticryptococcal
delayed-type hypersensitivity, and high levels of serum IgE. These
results demonstrate that expression of CCR2 is required for the
development of a T1-type response to C. neoformans
infection and lack of CCR2 results in a switch to a T2-type response.
Thus, CCR2 plays a critical role in promoting the development of T1-
over T2-type immune responses in the lung following cryptococcus
infection.
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