Reduced IL-1β production in diet-induced obese mice impairs host defense against skin Staphylococcus aureus infection

Abstract

    Obesity leads to a state of chronic inflammation associated with increased levels of proinflammatory cytokines including interleukin-1β (IL-1β) that plays a critical role in host defense against Staphylococcus aureus infection. In this study, we investigated host defense against skin S. aureus infection in high-fat diet (HFD)-induced non-diabetic obesity by focusing on IL-1β production from subcutaneous adipose tissue derived-macrophages (SATDMs). Bacterial numbers in skin lesions of HFD-fed mice were higher than those of normal-fat diet (ND)-fed control mice on day 3 after subcutaneous S. aureus infection. IL-1β production from SATDMs of HFD-fed mice was less than that of ND-fed mice after stimulation with formalin-killed S. aureus and ATP. In addition, NLRP3 mRNA expression and protein level of activated caspase-1 in SATDMs of HFD-fed mice were lower than those of ND-fed mice after stimulation. Conversely, IL-1β production, NLRP3 mRNA expression and protein level of activated caspase-1 from visceral adipose tissue-derived macrophages of HFD-fed mice were higher than those of ND-fed mice. These results suggest that reduced IL-1β production in SATDMs of HFD-fed obese mice might be involved in impairment of host defense against skin S. aureus infection.