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

Abstract

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-1alpha (MIP-1alpha), CCL4/MIP-1beta, and CCL5/regulated on activation, normal T expressed and secreted (RANTES), all chemokines binding to these two receptors. The CCL3/MIP-1alpha-induced shifts of intracellular calcium concentrations declined gradually to almost undetectable levels, and most conspiciuously, the chemotactic response to CCL3/MIP-1alpha, CCL4/MIP-1beta, 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.

A macrophage subpopulation recruited by CC chemokine ligand-2 clears apoptotic cells in noninfectious lung injury

“…Most importantly, we identified that DI cells recruited by overexpression of Ccl2 play a role in clearance of apoptotic cells and promote resolution of inflammation after noninfectious lung injury. Previous reports demonstrated that CCL2 was upregulated during infectious (42) and noninfectious lung injury (5,10,41,52). CCL2 has been showed to induce leukocyte infiltration during inflammation (8,38,39,43).…”

“Host Tissue Damage” Signal ATP Promotes Non-directional Migration and Negatively Regulates Toll-like Receptor Signaling in Human Monocytes

“…After 3 min, cells were lysed using a protein extraction reagent (M-PER, Pierce Biotechnology), supplemented with a protease inhibitor mixture (Complete, Roche Diagnostics). Phosphorylation of Akt was then assayed by Western blot as recently described (21). Equal loading was controlled by detecting total Akt.…”

“…Infection with Influenza A Virus-Influenza A/PR/8 (H1N1) virus was propagated and purified as previously described (21,22). Viral titers were determined by plaque assay, and monocytes were infected with H1N1 virus at a multiplicity of infection of 2.…”

Measles virus modulates chemokine release and chemotactic responses of dendritic cells

“…DC chemotaxis is targeted during immune evasion by vaccinia virus, human cytomegalovirus (HCMV), herpes simplex virus (HSV) and influenza A virus (Humrich et al, 2007;Moutaftsi et al, 2004;Prechtel et al, 2005;Salentin et al, 2003;Varani et al, 2005), but it is not known whether MV modulates these properties too.…”