Investigation of mechanisms involved in phagocytosis of Legionella pneumophila by human cells

Abstract

Legionella pneumophila, the causative agent of Legionnaires' disease, is able to survive and multiply efficiently in a variety of mammalian cells. By using in vitro assays, the uptake of L. pneumophila into monocytes has shown to be mediated, at least in part, through attachment of complement-coated bacteria to complement receptors, but complement-independent phagocytosis could also be demonstrated. Since complement levels in the human lung are normally low, the role of complement-dependent phagocytosis in the pathogenesis of Legionnaires' disease is doubtful. However, the contribution of other potential phagocytosis-related host cell surface molecules to the phagocytosis of L. pneumophila has never been investigated. We therefore analyzed the role of complement receptors 1 (CD35) and 3 (CD11b/18), the lipopolysaccharide (LPS) receptor (CD14), the L 1 -integrin chain of the fibronectin receptor (CD29), the intercellular adhesion molecule 1 (ICAM-1, CD54) and the transferrin receptor (CD71) in the complement-independent uptake of L. pneumophila. To exclude any influence of culture conditions onto phagocytosis rates, we compared a fresh clinical isolate with an agaradapted isolate of L. pneumophila. In addition, we used three different host cell types (MM6, HeLa and Jurkat cells) expressing different rates of complement receptors. We could show that both strains of L. pneumophila were phagocytized by the three host cell lines to the same extent, but intracellular multiplication was only found in MM6 and, although to a much lesser degree, in Jurkat cells. Preincubation of MM6 cells with monoclonal antibodies directed against the above cited phagocytosis-related receptors did not result in inhibition of L. pneumophila uptake. We therefore conclude that typical phagocytosis-related cell surface receptors are not involved in the complementindependent phagocytosis of L. pneumophila. ß

Molecular characterization of Legionella pneumophila-induced interleukin-8 expression in T cells

“…However, recent studies have shown that L. pneumophila replicates also in human alveolar epithelial cells [5,6]. Although Legionella less efficiently replicates within human T cells compared with macrophages [7], little is known of the consequences of T cell infection with Legionella .…”

Molecular Pathogenesis of Infections Caused byLegionella pneumophila

“…The relevance of opsonin-dependent phagocytosis to L. pneumophila infection is also dubious, given that complement levels in the lungs are generally very low (274). In addition, the phagocytosis of L. pneumophila is clearly observed in the absence of serum and occurs in cells that express complement receptors at only low levels (146,281,354). Furthermore, the ability of L. pneumophila to invade nonprofessional phagocytes such as A549, CHO-K1, and HeLa epithelial cells supports the hypothesis that the uptake of L. pneumophila is a virulence-directed property of the pathogen (112,139,222,250).…”

UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance

“…The expression of CD15 was decreased during differentiation with TGFβ and calcitriol, but was not influenced by miRNA-328 knockdown. Finally, we measured CD11b expression which represents a marker for mature myeloid cells29. The analysis revealed a strong upregulation of the CD11b marker during MM6 cell differentiation which was significantly reduced by miRNA-328 knockdown (Fig.…”