Differential Induction of Inflammatory Cytokines and Reactive Oxygen Species in Murine Peritoneal Macrophages and Reside
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Differential Induction of Inflammatory Cytokines and Reactive Oxygen Species in Murine Peritoneal Macrophages and Resident Fresh Bone Marrow Cells by Acute Staphylococcus aureus Infection: Contribution of Toll-Like Receptor 2 (TLR2) Ajeya Nandi,1 Somrita Dey,1 Julie Biswas,1 Pooja Jaiswal,1 Shamreen Naaz,1 Tamima Yasmin,1 and Biswadev Bishayi1,2
Abstract—Among the known Toll-like receptors (TLRs), Toll-like receptor 2 (TLR2) is a key sensor for detecting Staphylococcus aureus invasion. But the function of TLR2 during S. aureus infection in different cell populations is unclear. Two different cell subtypes were chosen to study the interaction of S. aureus with TLR2 because macrophages are extremely different from one compartment to another and their capacity to respond to live bacteria or bacterial products differs from one site to another. The contribution of TLR2 to the host innate response against acute live S. aureus infection and heat-killed S. aureus (HKSA) using anti-TLR2 antibody in murine peritoneal macrophages and resident fresh bone marrow cells has been investigated here. TLR2 blocking before infection induces the release of interleukin (IL)-10 by macrophages thereby inhibiting excessive production of oxidants by activating antioxidant enzymes. TLR2-blocked peritoneal macrophages showed impaired release of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and IL-6 in response to both live and heat-killed S. aureus infection except bone marrow cells. TLR2-mediated free radical production and killing of S. aureus were modulated by TLR2 blocking in peritoneal macrophages and resident bone marrow cells. This study supported that S. aureus persists in resident bone marrow cells in a state of quiescence. KEY WORDS: antioxidant enzymes; bone marrow cells; intracellular survival; murine peritoneal macrophages; Staphylococcus aureus; Swiss albino mice; Toll-like receptor 2.
INTRODUCTION Staphylococcus aureus is a major pathogen that causes a variety of diseases ranging from minor skin 1
Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, APC Road, Calcutta, 700009West Bengal, India 2 To whom correspondence should be addressed at Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, APC Road, Calcutta, 700009West Bengal, India. Email: [email protected] Abbreviations: CPCSEA, Committee for the Purpose of Control and S u p e r v i s i o n o f E x p e r i m e n t s o n A n i m a l ; E D TA , Ethylenediaminetetraacetic acid; FBMCs, Fresh bone marrow cells; FBS, Fetal bovine serum; HBSS, Hank’s balanced salt solution; iNOS, Inducible nitric oxide synthase; NaNO3, Sodium nitrate; NaOH, Sodium hydroxide; NaCl, Sodium chloride; PAMP, Pathogen-associated molecular pattern; TLR2, Toll-like receptor 2; TLRs, Toll-like receptors
infections to severe systemic complications such as bacteraemia, septic shock, septic arthritis and osteomyelitis often with fatal results [1]. S. au
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