Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation

Ananda S. Mirchandani; Stephen J. Jenkins; Calum C. Bain; Manuel A. Sanchez-Garcia; Hannah Lawson; Patricia Coelho; Fiona Murphy; David M. Griffith; Ailiang Zhang; Tyler Morrison; Tony Ly; Simone Arienti; Pranvera Sadiku; Emily R. Watts; Rebecca S. Dickinson; Leila Reyes; George Cooper; Sarah Clark; David Lewis; Van Kelly; Christos Spanos; Kathryn M. Musgrave; Liam Delaney; Isla Harper; Jonathan Scott; Nicholas J. Parkinson; Anthony J. Rostron; J. Kenneth Baillie; Sara Clohisey; Clare Pridans; Lara Campana; Philip Starkey Lewis; A. John Simpson; David H. Dockrell; Jürgen Schwarze; Nikhil Hirani; Peter J. Ratcliffe; Christopher W. Pugh; Kamil Kranc; Stuart J. Forbes; Moira K.B. Whyte; Sarah R. Walmsley

doi:10.1038/s41590-022-01216-z

Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation

Ananda S. Mirchandani^*, Stephen J. Jenkins, Calum C. Bain, Manuel A. Sanchez-Garcia, Hannah Lawson, Patricia Coelho, Fiona Murphy, David M. Griffith, Ailiang Zhang, Tyler Morrison, Tony Ly, Simone Arienti, Pranvera Sadiku, Emily R. Watts, Rebecca S. Dickinson, Leila Reyes, George Cooper, Sarah Clark, David Lewis, Van KellyChristos Spanos, Kathryn M. Musgrave, Liam Delaney, Isla Harper, Jonathan Scott, Nicholas J. Parkinson, Anthony J. Rostron, J. Kenneth Baillie, Sara Clohisey, Clare Pridans, Lara Campana, Philip Starkey Lewis, A. John Simpson, David H. Dockrell, Jürgen Schwarze, Nikhil Hirani, Peter J. Ratcliffe, Christopher W. Pugh, Kamil Kranc, Stuart J. Forbes, Moira K.B. Whyte, Sarah R. Walmsley

^*Corresponding author for this work

Strathclyde Institute Of Pharmacy And Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

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Abstract

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

Original language	English
Pages (from-to)	927-939
Number of pages	13
Journal	Nature Immunology
Volume	23
Issue number	6
Early online date	27 May 2022
DOIs	https://doi.org/10.1038/s41590-022-01216-z
Publication status	Published - 30 Jun 2022

Keywords

hypoxaemia
lung injury
persistent inflammation

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Mirchandani-etal-NI-2023-Hypoxia-shapes-the-immune-landscapeFinal published version, 8.66 MBLicence: CC BY 4.0

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Author correction: Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation
Mirchandani, A. S., Jenkins, S. J., Bain, C. C., Sanchez-Garcia, M. A., Lawson, H., Coelho, P., Murphy, F., Griffith, D. M., Zhang, A., Morrison, T., Ly, T., Arienti, S., Sadiku, P., Watts, E. R., Dickinson, R. S., Reyes, L., Cooper, G., Clark, S., Lewis, D., Kelly, V., & 22 othersSpanos, C., Musgrave, K. M., Delaney, L., Harper, I., Scott, J., Parkinson, N. J., Rostron, A. J., Baillie, J. K., Clohisey, S., Pridans, C., Campana, L., Lewis, P. S., Simpson, A. J., Dockrell, D. H., Schwarze, J., Hirani, N., Ratcliffe, P. J., Pugh, C. W., Kranc, K., Forbes, S. J., Whyte, M. K. B. & Walmsley, S. R., 19 Jul 2022, In: Nature Immunology. 23, 1 p., 1394.
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Mirchandani, A. S., Jenkins, S. J., Bain, C. C., Sanchez-Garcia, M. A., Lawson, H., Coelho, P., Murphy, F., Griffith, D. M., Zhang, A., Morrison, T., Ly, T., Arienti, S., Sadiku, P., Watts, E. R., Dickinson, R. S., Reyes, L., Cooper, G., Clark, S., Lewis, D., ... Walmsley, S. R. (2022). Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation. Nature Immunology, 23(6), 927-939. https://doi.org/10.1038/s41590-022-01216-z

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title = "Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation",

abstract = "Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.",

keywords = "hypoxaemia, lung injury, persistent inflammation",

author = "Mirchandani, {Ananda S.} and Jenkins, {Stephen J.} and Bain, {Calum C.} and Sanchez-Garcia, {Manuel A.} and Hannah Lawson and Patricia Coelho and Fiona Murphy and Griffith, {David M.} and Ailiang Zhang and Tyler Morrison and Tony Ly and Simone Arienti and Pranvera Sadiku and Watts, {Emily R.} and Dickinson, {Rebecca S.} and Leila Reyes and George Cooper and Sarah Clark and David Lewis and Van Kelly and Christos Spanos and Musgrave, {Kathryn M.} and Liam Delaney and Isla Harper and Jonathan Scott and Parkinson, {Nicholas J.} and Rostron, {Anthony J.} and Baillie, {J. Kenneth} and Sara Clohisey and Clare Pridans and Lara Campana and Lewis, {Philip Starkey} and Simpson, {A. John} and Dockrell, {David H.} and J{\"u}rgen Schwarze and Nikhil Hirani and Ratcliffe, {Peter J.} and Pugh, {Christopher W.} and Kamil Kranc and Forbes, {Stuart J.} and Whyte, {Moira K.B.} and Walmsley, {Sarah R.}",

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Mirchandani, AS, Jenkins, SJ, Bain, CC, Sanchez-Garcia, MA, Lawson, H, Coelho, P, Murphy, F, Griffith, DM, Zhang, A, Morrison, T, Ly, T, Arienti, S, Sadiku, P, Watts, ER, Dickinson, RS, Reyes, L, Cooper, G, Clark, S, Lewis, D, Kelly, V, Spanos, C, Musgrave, KM, Delaney, L, Harper, I, Scott, J, Parkinson, NJ, Rostron, AJ, Baillie, JK, Clohisey, S, Pridans, C, Campana, L, Lewis, PS, Simpson, AJ, Dockrell, DH, Schwarze, J, Hirani, N, Ratcliffe, PJ, Pugh, CW, Kranc, K, Forbes, SJ, Whyte, MKB & Walmsley, SR 2022, 'Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation', Nature Immunology, vol. 23, no. 6, pp. 927-939. https://doi.org/10.1038/s41590-022-01216-z

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AU - Mirchandani, Ananda S.

AU - Jenkins, Stephen J.

AU - Bain, Calum C.

AU - Sanchez-Garcia, Manuel A.

AU - Lawson, Hannah

AU - Coelho, Patricia

AU - Murphy, Fiona

AU - Griffith, David M.

AU - Zhang, Ailiang

AU - Morrison, Tyler

AU - Ly, Tony

AU - Arienti, Simone

AU - Sadiku, Pranvera

AU - Watts, Emily R.

AU - Dickinson, Rebecca S.

AU - Reyes, Leila

AU - Cooper, George

AU - Clark, Sarah

AU - Lewis, David

AU - Kelly, Van

AU - Spanos, Christos

AU - Musgrave, Kathryn M.

AU - Delaney, Liam

AU - Harper, Isla

AU - Scott, Jonathan

AU - Parkinson, Nicholas J.

AU - Rostron, Anthony J.

AU - Baillie, J. Kenneth

AU - Clohisey, Sara

AU - Pridans, Clare

AU - Campana, Lara

AU - Lewis, Philip Starkey

AU - Simpson, A. John

AU - Dockrell, David H.

AU - Schwarze, Jürgen

AU - Hirani, Nikhil

AU - Ratcliffe, Peter J.

AU - Pugh, Christopher W.

AU - Kranc, Kamil

AU - Forbes, Stuart J.

AU - Whyte, Moira K.B.

AU - Walmsley, Sarah R.

PY - 2022/6/30

Y1 - 2022/6/30

N2 - Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

AB - Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

KW - hypoxaemia

KW - lung injury

KW - persistent inflammation

U2 - 10.1038/s41590-022-01216-z

DO - 10.1038/s41590-022-01216-z

M3 - Article

C2 - 35624205

AN - SCOPUS:85130791312

SN - 1529-2908

VL - 23

SP - 927

EP - 939

JO - Nature Immunology

JF - Nature Immunology

IS - 6

ER -

Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation

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Author correction: Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation

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