Role of complement component C1q in phagocytosis of Listeria monocytogenes by murine macrophage-like cell lines.
Listeria monocytogenes is a facultative intracellular pathogen of a great variety of cells. Among them, macrophages constitute the major effector cells of listerial immunity during the course of an infection. Although the molecular bases of L. monocytogenes attachment and entry to phagocytes are not completely understood, it has been demonstrated that C3b significantly increases L. monocytogenes uptake by macrophages via complement receptor type 3. The first component of complement, C1q, is present in organic fluids at a relatively high concentration, and C1q receptor sites in macrophages are also abundant. In the present report, results of studies on the role of C1q in the internalization and infectivity of L. monocytogenes by macrophages are presented. L. monocytogenes uptake is enhanced by prior treatment of bacteria with normal sera. Heated serum or C1q-deficient serum abrogates this enhancement. Purified C1q specifically restored uptake. This effect was blocked by the addition of F(ab')2 anti-C1q antibody but not by an irrelevant matched antibody. Direct binding of C1q to L. monocytogenes was specific, saturable, and dose dependent with both fluorescent and radiolabeled C1q. N-Acetyl-D-alanyl-L-isoglutamine, diaminopimelic acid, and L-rhamnose caused a significant dose-dependent inhibition of C1q binding to bacteria, suggesting that these molecules, at least, are involved in the attachment of C1q to L. monocytogenes cell wall. When C1q binding structures on macrophage-like cells were blocked with saturating concentrations of C1q, the uptake of C1q-opsonized bacteria was less than in untreated cells. These experiments demonstrate that, in addition to other reported mechanisms, L. monocytogenes binds C1q, which mediates enhanced uptake by macrophages through C1q binding structures.
Alvarez-Dominguez
C
C
Servicio de Immunología, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
Carrasco-Marin
E
E
Leyva-Cobian
F
F
D000818:Animals; D002352:Carrier Proteins; D002460:Cell Line; D015922:Complement C1q / Q000276:immunology*; D006801:Humans; D018960:Hyaluronan Receptors; D008089:Listeria monocytogenes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice; D024101:Mitochondrial Proteins; D010587:Phagocytosis; D011951:Receptors, Complement / Q000502:physiology
C087299:C1QBP protein, human; C490193:C1qbp protein, mouse; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D015922:Complement C1q