Activation of murine macrophages by Neisseria meningitidis and IFN-gamma in vitro: distinct roles of class A scavenger and Toll-like pattern recognition receptors in selective modulation of surface phenotype.

Journal article

Innate and adaptive immune activation of macrophages (Mphi) by microorganisms and antigen-activated lymphoid cells, respectively, plays an important role in host defense and immunopathology. Antigen-presenting cells express a range of pattern recognition receptors including the class A types I and II scavenger receptors (SR-A) and Toll-like receptors (TLR). Recognition of microbial products by SR-A and TLR controls uptake, killing, altered gene expression, and the adaptive immune response; however, the contribution of each receptor and interplay with cytokine stimuli such as interferon-gamma (IFN-gamma) are not defined. We used Neisseria meningitidis (NM), a potent activator of innate immunity, and IFN-gamma, a prototypic T helper cell type 1 proinflammatory cytokine, to compare surface antigens, secretion of mediators, and receptor functions in elicited peritoneal Mphi from wild-type and genetically modified mouse strains. We show that these stimuli regulate major histocompatibility complex type II (MHC-II) and costimulatory molecules differentially, as well as expression of the mannose receptor and of Mphi receptor with collagenous structure (MARCO), a distinct SR-A, which provides a selective marker for innate activation. In combination, NM inhibited up-regulation of MHC-II by IFN-gamma while priming enhanced release of tumor necrosis factor alpha and nitric oxide. The SR-A contributes to phagocytosis of the organisms but not to their ability to induce CD80, CD86, and MARCO or to inhibit MHC-II. Conversely, studies with lipopolysaccharide (LPS)-deficient organisms and/or TLR-4 mutant mice showed that LPS and TLR-4 are at least partially required to induce CD80, CD86, and MARCO, but LPS is not required to inhibit MHC-II. These studies provide an experimental model and identify surface markers for analysis of innate and acquired immune activation of Mphi.

Authors: Mukhopadhyay, S; Peiser, L; Gordon, S

• Publication status: Published
• Journal: Journal of leukocyte biology
• Volume: 76
• Issue: 3
• Pages: 577-584
• Publication date: 2004-09-01
• DOI: 10.1189/jlb.0104014
• EISSN: 1938-3673
• ISSN: 0741-5400
• Language: English
• Keywords: Mice, Knockout; Interferon-gamma; Up-Regulation; Immunity, Innate; Neisseria meningitidis; Mice; Toll-Like Receptors; Toll-Like Receptor 4; Membrane Glycoproteins; Phenotype; Mannose-Binding Lectins; Histocompatibility Antigens Class II; Chemotaxis, Leukocyte; Lipopolysaccharides; Receptors, Cell Surface; Scavenger Receptors, Class A; Macrophages; Lectins, C-Type; Antigens, CD; Inflammation Mediators; Antigens, CD86; Receptors, Immunologic; Antigens, CD80; Animals; Tumor Necrosis Factor-alpha; Antigens, CD36