Chemokine receptor expression and chemotactic responsiveness of human monocytes after influenza A virus infection

Journal of Leukocyte Biology

Diethard Gemsa²  Hans Sprenger¹  Robert Salentin²  Andreas Kaufmann² 

[1] Institute of Laboratory Medicine, Leopoldina-Hospital, Schweinfurt, Germany Institute of Laboratory Medicine, Leopoldina-Hospital, Schweinfurt, Germany Institute of Laboratory Medicine, Leopoldina-Hospital, Schweinfurt, Germany;Institute of Immunology, Philipps University, Marburg, Germany; and Institute of Immunology, Philipps University, Marburg, Germany; and Institute of Immunology, Philipps University, Marburg, Germany; and

关键词: chemokines;    migration;    monocytes/macrophages;   

DOI  :  10.1189/jlb.1102565

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Chemokines and their receptors play an important role in site-directed migration and activation of leukocytes. To understand how viral infections may impair this function, we analyzed chemokine receptor expression and responsiveness of human monocytes after infection with influenza A virus. Whereas treatment with infectious virus induced a rapid down-regulation of the CCL2/monocyte chemoattractant protein-1 (MCP-1)-specific receptor CCR2, inactivated virus did not significantly alter CCR2 surface expression. In parallel, the response to CCL2/MCP-1 was lost after infection with active virus: Neither a CCL2/MCP-1-induced shift of intracellular calcium concentrations nor the chemotactic response to CCL2/MCP-1 was detectable. In striking contrast, the presence of CCR1 and CCR5 on the cell surface remained unchanged or was even slightly up-regulated after viral infection. However, the remaining expression of CCR1 and CCR5 correlated reciprocally with an ongoing unresponsiveness to the CCR1 and CCR5 agonists CCL3/macrophage-inflammatory protein-1α (MIP-1α), CCL4/MIP-1β, and CCL5/regulated on activation, normal T expressed and secreted (RANTES), all chemokines binding to these two receptors. The CCL3/MIP-1α-induced shifts of intracellular calcium concentrations declined gradually to almost undetectable levels, and most conspiciuously, the chemotactic response to CCL3/MIP-1α, CCL4/MIP-1β, and CCL5/RANTES was lost after infection with active influenza virus. Inactivated virus particles did not significantly alter the responsiveness induced by CCR1 and CCR5 agonists. Despite the inability of chemokine receptors to elicit migration, phosphorylation of protein kinase B was not altered in virus-infected monocytes. Thus, influenza A virus infection rapidly abolishes the functional responsiveness of monocytes and prevents an adequate response of the infected cells to chemokine stimulation.

【 授权许可】

Unknown