The role of monocyte chemotactic protein-1 (MCP-1) in the recruitment of monocytes and CD4+ T cells during a pulmonary Cryptococcus neoformans infection.

Abstract

Cryptococcus neoformans is acquired via the respiratory tract and is the leading cause of fatal mycosis in AIDS. Development of a T cell-mediated pulmonary inflammatory response is critical for clearance of this pathogen; however, the chemotactic factors that mediate inflammatory cell recruitment into the lungs have not been identified. In the present study, the bronchoalveolar lavage (BAL) fluid levels of the C-C chemokine monocyte chemotactic protein-1 (MCP-1) and the recruitment of inflammatory cells both increased following pulmonary infection with C. neoformans. The kinetics of MCP-1 production in the lungs correlated most closely with the recruitment of CD4+ T cells and monocytes/macrophages. Administration of neutralizing anti-MCP-1 Abs in vivo reduced the BAL fluid levels of MCP-1, decreased the recruitment of both macrophages (> 95%) and CD4+ T cells (76 +/- 9%), and inhibited cryptococcal clearance. Although no in vitro neutrophil or B cell chemotactic activity has been reported for MCP-1, recruitment of these leukocytes was also decreased in anti-MCP-1-treated mice (most likely an indirect effect of reducing the number of CD4+ T cells and macrophages). Neutralization of MCP-1 also resulted in decreased BAL fluid levels of TNF-alpha and IL-6. This is the first demonstration of a role for MCP-1 in clearance of an infection, and provides direct evidence that MCP-1 plays a critical role in the T cell-dependent immune response to C. neoformans.

• Authors: G B Huffnagle, R M Strieter, T J Standiford, R A McDonald, M D Burdick, S L Kunkel, G B Toews
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 155 Issue 10 Pg. 4790-7 (Nov 15 1995) ISSN: 0022-1767 [Print] United States
• PMID: 7594481 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Chemokine CCL2

Topics

• Animals
• Bronchoalveolar Lavage
• CD4-Positive T-Lymphocytes (immunology, pathology)
• Chemokine CCL2 (immunology)
• Chemotaxis
• Cryptococcosis (immunology, pathology)
• Female
• Immunity, Cellular
• Lung Diseases, Fungal (immunology, microbiology, pathology)
• Mice
• Mice, Inbred CBA
• Monocytes (immunology, pathology)