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Inflammatory Monocytes and Subsets of Macrophages with Distinct Surface Phenotype Correlate with Specific Integrin Expression Profile during Murine Sepsis

Shiba Prasad Dash, Papiya Chakraborty and Pranita P. Sarangi
J Immunol December 1, 2021, 207 (11) 2841-2855; DOI: https://doi.org/10.4049/jimmunol.2000821
Shiba Prasad Dash
Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
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Papiya Chakraborty
Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
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Pranita P. Sarangi
Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
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Key Points

  • Tissue homing Ly-6Chi monocytes express integrin α4 during systemic inflammation.

  • Macrophages demonstrate an immunosuppressive phenotype in the lungs.

  • F4/80+CD206hi macrophages express a high level of integrin αv and TGFBR1.

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Abstract

Monocytes and macrophages participate in both pro- and anti-inflammatory responses during sepsis. Integrins are the cell adhesion receptors that mediate leukocyte migration and functions. To date, it is not known whether integrin profiles correlate with their trafficking, differentiation, and polarization during sepsis. In this study, using endotoxemia and cecal ligation and puncture model of murine sepsis, we have analyzed the role of surface integrins in tissue-specific infiltration, distribution of monocytes and macrophages, and their association with inflammation-induced phenotypic and functional alterations postinduction (p.i.) of sepsis. Our data show that Ly-6Chi inflammatory monocytes infiltrated into the peritoneum from blood and bone marrow within a few hours p.i. of sepsis, with differential distribution of small (Ly-6CloCD11bloF4/80lo) and large peritoneal macrophages (Ly-6CloCD11bhiF4/80hi) in both models. The results from flow cytometry studies demonstrated a higher expression of integrin α4β1 on the Ly-6Chi monocytes in different tissues, whereas macrophages in the peritoneum and lungs expressed higher levels of integrin α5β1 and αvβ3 in both models. Additionally, F4/80+ cells with CD206hiMHCIIlo phenotype increased in the lungs of both models by six hours p.i. and expressed higher levels of integrin αvβ3 in both lungs and peritoneum. The presence of such cells correlated with higher levels of IL-10 and lower levels of IL-6 and IL-1β transcripts within six hours p.i. in the lungs compared with the mesentery. Furthermore, bioinformatic analysis with its experimental validation revealed an association of integrin α4 and α5 with inflammatory (e.g., p-SRC) and integrin αv with regulatory molecules (e.g., TGFBR1) in macrophages during sepsis.

Footnotes

  • This work was supported by the Department of Biotechnology, Ministry of Science and Technology, Government of India (102/IFD/SAN/1671/2014-2015 and BT/010/IYBA/2017/04) to P.P.S., a University Grants Commission, Government of India fellowship to S.P.D. (Sr. No-2061430670), and a Ministry of Human Resource Development, Government of India fellowship to P.C. (02-23-200-429).

  • S.P.D. and P.C. performed the experiments and analyzed the data. P.P.S. conceived and directed the study. S.P.D. and P.P.S. wrote the manuscript.

  • Abbreviations used in this article

    CLP
    cecal ligation and puncture
    ECM
    extracellular matrix
    LPM
    large peritoneal macrophage
    MFI
    mean fluorescence intensity
    MHCII
    MHC class II
    p.i.
    postinduction
    SPM
    small peritoneal macrophage
    STRING
    Search Tool for the Retrieval of Interacting Genes/Proteins

  • Received July 14, 2020.
  • Accepted September 27, 2021.
  • Copyright © 2021 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 207 (11)
The Journal of Immunology
Vol. 207, Issue 11
1 Dec 2021
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Inflammatory Monocytes and Subsets of Macrophages with Distinct Surface Phenotype Correlate with Specific Integrin Expression Profile during Murine Sepsis
Shiba Prasad Dash, Papiya Chakraborty, Pranita P. Sarangi
The Journal of Immunology December 1, 2021, 207 (11) 2841-2855; DOI: 10.4049/jimmunol.2000821

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Inflammatory Monocytes and Subsets of Macrophages with Distinct Surface Phenotype Correlate with Specific Integrin Expression Profile during Murine Sepsis
Shiba Prasad Dash, Papiya Chakraborty, Pranita P. Sarangi
The Journal of Immunology December 1, 2021, 207 (11) 2841-2855; DOI: 10.4049/jimmunol.2000821
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