Calcium Dynamics Regulate Protective Responses and Growth of Staphylococcus aureus in Macrophages
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 calciu...
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doaj-a636c811913c401686492634e6e26cef2021-09-05T20:42:36ZengDe GruyterBiomolecular Concepts1868-50211868-503X2020-12-0111123023910.1515/bmc-2020-0021Calcium Dynamics Regulate Protective Responses and Growth of Staphylococcus aureus in MacrophagesVerma Chaitenya0Rana Ankush Kumar1Anang Vandana2Tiwari Brijendra K3Singh Aayushi4Saraswati Shakuntala Surender Kumar5Shariff Malini6Natarajan Krishnamurthy7Infectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi110007, IndiaInfectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi110007, IndiaInfectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi110007, IndiaInfectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi110007, IndiaInfectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi110007, IndiaInfectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi110007, IndiaDepartment of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi110007, IndiaInfectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi110007, IndiaStaphylococcus 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.https://doi.org/10.1515/bmc-2020-0021calciumstaphylococcus aureust-cellautophagyphagolysosome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Verma Chaitenya Rana Ankush Kumar Anang Vandana Tiwari Brijendra K Singh Aayushi Saraswati Shakuntala Surender Kumar Shariff Malini Natarajan Krishnamurthy |
spellingShingle |
Verma Chaitenya Rana Ankush Kumar Anang Vandana Tiwari Brijendra K Singh Aayushi Saraswati Shakuntala Surender Kumar Shariff Malini Natarajan Krishnamurthy Calcium Dynamics Regulate Protective Responses and Growth of Staphylococcus aureus in Macrophages Biomolecular Concepts calcium staphylococcus aureus t-cell autophagy phagolysosome |
author_facet |
Verma Chaitenya Rana Ankush Kumar Anang Vandana Tiwari Brijendra K Singh Aayushi Saraswati Shakuntala Surender Kumar Shariff Malini Natarajan Krishnamurthy |
author_sort |
Verma Chaitenya |
title |
Calcium Dynamics Regulate Protective Responses and Growth of Staphylococcus aureus in Macrophages |
title_short |
Calcium Dynamics Regulate Protective Responses and Growth of Staphylococcus aureus in Macrophages |
title_full |
Calcium Dynamics Regulate Protective Responses and Growth of Staphylococcus aureus in Macrophages |
title_fullStr |
Calcium Dynamics Regulate Protective Responses and Growth of Staphylococcus aureus in Macrophages |
title_full_unstemmed |
Calcium Dynamics Regulate Protective Responses and Growth of Staphylococcus aureus in Macrophages |
title_sort |
calcium dynamics regulate protective responses and growth of staphylococcus aureus in macrophages |
publisher |
De Gruyter |
series |
Biomolecular Concepts |
issn |
1868-5021 1868-503X |
publishDate |
2020-12-01 |
description |
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. |
topic |
calcium staphylococcus aureus t-cell autophagy phagolysosome |
url |
https://doi.org/10.1515/bmc-2020-0021 |
work_keys_str_mv |
AT vermachaitenya calciumdynamicsregulateprotectiveresponsesandgrowthofstaphylococcusaureusinmacrophages AT ranaankushkumar calciumdynamicsregulateprotectiveresponsesandgrowthofstaphylococcusaureusinmacrophages AT anangvandana calciumdynamicsregulateprotectiveresponsesandgrowthofstaphylococcusaureusinmacrophages AT tiwaribrijendrak calciumdynamicsregulateprotectiveresponsesandgrowthofstaphylococcusaureusinmacrophages AT singhaayushi calciumdynamicsregulateprotectiveresponsesandgrowthofstaphylococcusaureusinmacrophages AT saraswatishakuntalasurenderkumar calciumdynamicsregulateprotectiveresponsesandgrowthofstaphylococcusaureusinmacrophages AT shariffmalini calciumdynamicsregulateprotectiveresponsesandgrowthofstaphylococcusaureusinmacrophages AT natarajankrishnamurthy calciumdynamicsregulateprotectiveresponsesandgrowthofstaphylococcusaureusinmacrophages |
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1717785422140014592 |