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PMID: 10854218 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus.

The American journal of pathology ·Vol. 156 ·No. 6 ·2000-06-00 ·Pages 1951-9

Dawson TC, Beck MA, Kuziel WA, Henderson F, Maeda N

Abstract

The immune response to influenza A virus is characterized by an influx of both macrophages and T lymphocytes into the lungs of the infected host, accompanied by induced expression of a number of CC chemokines. CC chemokine receptors CCR5 and CCR2 are both expressed on activated macrophages and T cells. We examined how the absence of these chemokine receptors would affect pulmonary chemokine expression and induced leukocyte recruitment by infecting CCR5-deficient mice and CCR2-deficient mice with a mouse-adapted strain of influenza A virus. CCR5(-/-) mice displayed increased mortality rates associated with acute, severe pneumonitis, whereas CCR2(-/-) mice were protected from the early pathological manifestations of influenza because of defective macrophage recruitment. This delay in macrophage accumulation in CCR2(-/-) mice caused a subsequent delay in T cell migration, which correlated with high pulmonary viral titers at early time points. Infected CCR5(-/-) mice and CCR2(-/-) mice both exhibited increased expression of the gene for MCP-1, the major ligand for CCR2(-/-) and a key regulator of induced macrophage migration. These studies illustrate the very different roles that CCR5 and CCR2 play in the macrophage response to influenza infection and demonstrate how defects in macrophage recruitment affect the normal development of the cell-mediated immune response.

MeSH Terms
Animals Chemokine CCL2/physiology Influenza A virus/isolation & purification Lung/pathology Macrophages/physiology Mice Orthomyxoviridae Infections/mortality,pathology,physiopathology,virology Pneumonia/mortality,pathology,physiopathology,virology Receptors, CCR2 Receptors, CCR5/deficiency Receptors, Chemokine/deficiency Survival Analysis T-Lymphocytes/physiology Time Factors
Chemicals
Ccr2 protein, mouse Chemokine CCL2 Receptors, CCR2 Receptors, CCR5 Receptors, Chemokine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Dawson T C
Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7525, USA.
Beck M A
Kuziel W A
Henderson F
Maeda N
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)65068-7
Published
2000-06-00
Pages
1951-9
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1850091
Subset
IM
Grants
NHLBI NIH HHS · R01 HL042630 · United States
NHLBI NIH HHS · R37 HL042630 · United States
NHLBI NIH HHS · HL42630 · United States
NHLBI NIH HHS · HL54123 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)65068-7 PMC Full Text View journal details
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