MerTK Does Not Mediate Phagocytosis of Staphylococcus aureus but Attenuates Inflammation Induced by Staphylococcal Lipot
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ORIGINAL ARTICLE
MerTK Does Not Mediate Phagocytosis of Staphylococcus aureus but Attenuates Inflammation Induced by Staphylococcal Lipoteichoic Acid Through Blocking NF-κB Activation Bing Zhang,1 Huimei Wu,2 Lei Fang,2 Peishan Ding,2 Ke Xu,2 Qingbin Yang,1 and Rongyu Liu2,3
Abstract—Mer receptor tyrosine kinase (MerTK) expressed in macrophages is essential for phagocytosis of apoptotic cells. Here, we investigate whether MerTK is involved in the phagocytosis of Staphylococcus aureus (S. aureus) and regulation of staphylococcal lipoteichoic acid (LTA)-induced inflammatory response in macrophages. We found that stimulating RAW264.7 macrophages with S. aureus activated multiple signaling pathways including toll-like receptor 2 (TLR2), scavenger receptor A (SR-A), and MerTK. Meanwhile, S. aureus stimulation also induced activation of proteins focal adhesion kinase (FAK) and Rac1, which are related to phagocytosis. Pretreatment with a specific Mer-blocking antibody significantly inhibited S. aureus-induced phosphorylation of MerTK, while it had no effect on S. aureus-induced activation of FAK and Rac1. Moreover, by confocal laser microscope, we observed that the antibody blockade of MerTK had little impact on the phagocytosis of S. aureus by RAW264.7 macrophages. Additionally, pretreatment with this antibody further promoted LTA-induced phosphorylation of nuclear factor κB (NF-κB) p65 subunit and production of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1β, and macrophage inflammatory protein-2 (MIP-2). Collectively, these results suggest that MerTK does not play an essential role in the phagocytosis of S. aureus but attenuates inflammation induced by staphylococcal LTA through blocking NFκB activation. KEY WORDS: MerTK; macrophages; S. aureus; phagocytosis; LTA; inflammation.
INTRODUCTION Staphylococcus aureus (S. aureus) is a Gram-positive and classical extracellular pathogen, widely distributed
1
Department of Respiration, Hefei Second People’s Hospital, Anhui Medical University, Heping Road 246, Hefei, Anhui 230022, People’s Republic of China 2 Department of Respiration, Anhui Geriatric Institute, First Affiliated Hospital, Anhui Medical University, Jixi Road 218, Hefei, Anhui 230022, People’s Republic of China 3 To whom correspondence should be addressed at Department of Respiration, Anhui Geriatric Institute, First Affiliated Hospital, Anhui Medical University, Jixi Road 218, Hefei, Anhui 230022, People’s Republic of China. E-mail: [email protected]
between humans and animals. Numerous studies have demonstrated its ability to invade various types of nonprofessional phagocytic host cells such as fibroblasts, epithelial and endothelial cells, and replicate intracellularly [1–4]. In humans, S. aureus causes a variety of illnesses including minor skin and soft tissue infections, endovascular infections, endocarditis, osteomyelitis, pneumonia, septic arthritis, and sepsis [5]. The innate immune response to pathogens represents the first line of defense against infectious diseases [6, 7]. Macrophages that
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