The Scavenger Receptor MARCO Is Required for Lung Defense against Pneumococcal Pneumonia and Inhaled Particles

Abstract

Alveolar macrophages (AMs) express the class A scavenger receptor macrophage receptor with collagenous structure (MARCO), but its role in vivo in lung defense against bacteria and environmental particles has not been studied. We used MARCO-deficient mice to directly test the in vivo role of AM MARCO in innate defense against pneumococcal infection and environmental particles. In a murine model of pneumococcal pneumonia, MARCO−/− mice displayed an impaired ability to clear bacteria from the lungs, increased pulmonary inflammation and cytokine release, and diminished survival. In vitro binding of Streptococcus pneumoniae and in vivo uptake of unopsonized particles by MARCO−/− AMs were dramatically impaired. MARCO−/− mice treated with the “inert” environmental particle TiO2 showed enhanced inflammation and chemokine expression, indicating that MARCO-mediated clearance of inert particles by AMs prevents inflammatory responses otherwise initiated by other lung cells. Our findings point to an important role of MARCO in mounting an efficient and appropriately regulated innate immune response against inhaled particles and airborne pathogens.

A regulatory role for macrophage class A scavenger receptors in TLR4‐mediated LPS responses

“…We further show that the receptors contribute to the clearance of NM and LM infections injected i.p., although they are not crucial for host defense in these infection models. Similarly, Arredouani et al challenged the MARCO À/À and SR-A À/À mice intranasally with Streptococcus pneumoniae or TiO2 particles, and found diminished bacterial and particle clearance by the alveolar macrophages in these KO mice [33,34]. Further, the conclusion that class A SR contribute to the microbial clearance upon infection is also supported by the findings in a study in which WT and SR-A À/À mice were challenged with Staphylococcus aureus [35].…”

SR-A/MARCO–mediated ligand delivery enhances intracellular TLR and NLR function, but ligand scavenging from cell surface limits TLR4 response to pathogens

“…10 Both receptors have been shown to bind a range of isolated microbial components [11][12][13][14] and intact Grampositive and Gram-negative organisms, 15,16 and their nonredundant role in host defense has been established in a variety of bacterial infection models. [17][18][19][20] Although SR-A and MARCO recognize a range of highly inflammatory ligands, these receptors by themselves are unable to initiate inflammatory signaling, which is usually triggered by sensing PRRs that share overlapping ligand repertoires. However, SR-A and MARCO have been implicated in the pathogenesis of a range of chronic and acute inflammatory pathologies, including atherosclerosis, Alzheimer disease, granuloma formation, and septic shock.…”

Collagenous Transmembrane Proteins: Recent Insights into Biology and Pathology*

“…In addition to one large 270-residue collagenous region, the extracellular C terminus of MARCO contains an SRCR domain involved in binding of Grampositive and -negative bacteria (10). MARCO is constitutively expressed in macrophages of the spleen and lymph nodes (54), and MARCO-mediated phagocytosis in the lung is essential for the innate defense against pneumococcal infection (55).…”