Abstract
Staphylococcus aureus (S. aureus) is a gram-positive bacteria, which causes various fatal respiratory infections including pneumonia. The emergence of Methicillin-Resistance Staphylococcus aureus (MRSA) demands a thorough understanding of host-pathogen interactions. Here we report the role of calcium in regulating defence responses of S. aureus in macrophages. Regulating calcium fluxes in cells by different routes differentially governs the expression of T cell costimulatory molecule CD80 and Th1 promoting IL-12 receptor. Inhibiting calcium influx from extracellular medium increased expression of IFN-γ and IL-10 while blocking calcium release from the intracellular stores inhibited TGF-β levels. Blocking voltage-gated calcium channels (VGCC) inhibited the expression of multiple cytokines. While VGCC regulated the expression of apoptosis protein Bax, extracellular calcium-regulated the expression of Cytochrome-C. Similarly, VGCC regulated the expression of autophagy initiator Beclin-1. Blocking VGCC or calcium release from intracellular stores promoted phagosome-lysosome fusion, while activating VGCC inhibited phagosomelysosome fusion. Finally, calcium homeostasis regulated intracellular growth of Staphylococcus, although using different mechanisms. While blocking extracellular calcium influx seems to rely on IFN-γ and IL-12Rβ receptor mediated reduction in bacterial survival, blocking either intracellular calcium release or via VGCC route seem to rely on enhanced autophagy mediated reduction of intracellular bacterial survival. These results point to fine-tuning of defence responses by routes of calcium homeostasis.
Highlights
Staphylococcus aureus (S. aureus) is a ubiquitous, grampositive bacterium
In mind in this paper, we investigated the role of calcium homeostasis in regulating defence responses to S. aureus infection in macrophages
We showed that is calcium important, but the route of calcium homeostasis played a determinant role in regulating many processes
Summary
Staphylococcus aureus (S. aureus) is a ubiquitous, grampositive bacterium. It is associated with a wide range of infections such as skin lesions (boils, sties) and localized abscess in other sites. In mind in this paper, we investigated the role of calcium homeostasis in regulating defence responses to S. aureus infection in macrophages. Our data show that similar to mycobacteria or Streptococcus calcium homeostasis regulated various aspects of macrophage responses to Staphylococcus aureus infection. Macrophages were incubated with different calcium modulators for 2h followed by infection with 20 MOI S. aureus infection for 2h and 24h.
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