Recruitment of dendritic cell progenitors to foci of influenza A virus infection sustains immunity

Mar Cabeza-Cabrerizo; Carlos M. Minutti; Mariana Pereira Da Costa; Ana Cardoso; Robert P. Jenkins; Justina Kulikauskaite; Michael D. Buck; Cécile Piot; Neil Rogers; Stefania Crotta; Lynne Whittaker; Hector Huerga Encabo; John W. McCauley; Judith E. Allen; Manolis Pasparakis; Andreas Wack; Erik Sahai; Caetano Reis E Sousa

doi:10.1126/sciimmunol.abi9331

Recruitment of dendritic cell progenitors to foci of influenza A virus infection sustains immunity

Mar Cabeza-Cabrerizo, Carlos M. Minutti, Mariana Pereira Da Costa, Ana Cardoso, Robert P. Jenkins, Justina Kulikauskaite, Michael D. Buck, Cécile Piot, Neil Rogers, Stefania Crotta, Lynne Whittaker, Hector Huerga Encabo, John W. McCauley, Judith E. Allen, Manolis Pasparakis, Andreas Wack, Erik Sahai, Caetano Reis E Sousa

Division of Immunology, Immunity to Infection and Respiratory Medicine

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

Abstract

Protection from infection with respiratory viruses such as influenza A virus (IAV) requires T cell-mediated immune responses initiated by conventional dendritic cells (cDCs) that reside in the respiratory tract. Here, we show that effective induction of T cell responses against IAV in mice requires reinforcement of the resident lung cDC network by cDC progenitors. We found that CCR2-binding chemokines produced during IAV infection recruit pre-cDCs from blood and direct them to foci of infection, increasing the number of progeny cDCs next to sites of viral replication. Ablation of CCR2 in the cDC lineage prevented this increase and resulted in a deficit in IAV-specific T cell responses and diminished resistance to reinfection. These data suggest that the homeostatic network of cDCs in tissues is insufficient for immunity and reveal a chemokine-driven mechanism of expansion of lung cDC numbers that amplifies T cell responses against respiratory viruses.

Original language	English
Article number	eabi9331
Journal	Science Immunology
Volume	6
Issue number	65
DOIs	https://doi.org/10.1126/sciimmunol.abi9331
Publication status	Published - Nov 2021

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Manchester Cancer Research Centre

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Cabeza-Cabrerizo, M., Minutti, C. M., Da Costa, M. P., Cardoso, A., Jenkins, R. P., Kulikauskaite, J., Buck, M. D., Piot, C., Rogers, N., Crotta, S., Whittaker, L., Encabo, H. H., McCauley, J. W., Allen, J. E., Pasparakis, M., Wack, A., Sahai, E., & Reis E Sousa, C. (2021). Recruitment of dendritic cell progenitors to foci of influenza A virus infection sustains immunity. Science Immunology, 6(65), Article eabi9331. https://doi.org/10.1126/sciimmunol.abi9331

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title = "Recruitment of dendritic cell progenitors to foci of influenza A virus infection sustains immunity",

abstract = "Protection from infection with respiratory viruses such as influenza A virus (IAV) requires T cell-mediated immune responses initiated by conventional dendritic cells (cDCs) that reside in the respiratory tract. Here, we show that effective induction of T cell responses against IAV in mice requires reinforcement of the resident lung cDC network by cDC progenitors. We found that CCR2-binding chemokines produced during IAV infection recruit pre-cDCs from blood and direct them to foci of infection, increasing the number of progeny cDCs next to sites of viral replication. Ablation of CCR2 in the cDC lineage prevented this increase and resulted in a deficit in IAV-specific T cell responses and diminished resistance to reinfection. These data suggest that the homeostatic network of cDCs in tissues is insufficient for immunity and reveal a chemokine-driven mechanism of expansion of lung cDC numbers that amplifies T cell responses against respiratory viruses.",

author = "Mar Cabeza-Cabrerizo and Minutti, {Carlos M.} and {Da Costa}, {Mariana Pereira} and Ana Cardoso and Jenkins, {Robert P.} and Justina Kulikauskaite and Buck, {Michael D.} and C{\'e}cile Piot and Neil Rogers and Stefania Crotta and Lynne Whittaker and Encabo, {Hector Huerga} and McCauley, {John W.} and Allen, {Judith E.} and Manolis Pasparakis and Andreas Wack and Erik Sahai and {Reis E Sousa}, Caetano",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved.",

year = "2021",

month = nov,

doi = "10.1126/sciimmunol.abi9331",

language = "English",

volume = "6",

journal = "Science Immunology",

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Cabeza-Cabrerizo, M, Minutti, CM, Da Costa, MP, Cardoso, A, Jenkins, RP, Kulikauskaite, J, Buck, MD, Piot, C, Rogers, N, Crotta, S, Whittaker, L, Encabo, HH, McCauley, JW, Allen, JE, Pasparakis, M, Wack, A, Sahai, E & Reis E Sousa, C 2021, 'Recruitment of dendritic cell progenitors to foci of influenza A virus infection sustains immunity', Science Immunology, vol. 6, no. 65, eabi9331. https://doi.org/10.1126/sciimmunol.abi9331

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AU - Cabeza-Cabrerizo, Mar

AU - Minutti, Carlos M.

AU - Da Costa, Mariana Pereira

AU - Cardoso, Ana

AU - Jenkins, Robert P.

AU - Kulikauskaite, Justina

AU - Buck, Michael D.

AU - Piot, Cécile

AU - Rogers, Neil

AU - Crotta, Stefania

AU - Whittaker, Lynne

AU - Encabo, Hector Huerga

AU - McCauley, John W.

AU - Allen, Judith E.

AU - Pasparakis, Manolis

AU - Wack, Andreas

AU - Sahai, Erik

AU - Reis E Sousa, Caetano

PY - 2021/11

Y1 - 2021/11

N2 - Protection from infection with respiratory viruses such as influenza A virus (IAV) requires T cell-mediated immune responses initiated by conventional dendritic cells (cDCs) that reside in the respiratory tract. Here, we show that effective induction of T cell responses against IAV in mice requires reinforcement of the resident lung cDC network by cDC progenitors. We found that CCR2-binding chemokines produced during IAV infection recruit pre-cDCs from blood and direct them to foci of infection, increasing the number of progeny cDCs next to sites of viral replication. Ablation of CCR2 in the cDC lineage prevented this increase and resulted in a deficit in IAV-specific T cell responses and diminished resistance to reinfection. These data suggest that the homeostatic network of cDCs in tissues is insufficient for immunity and reveal a chemokine-driven mechanism of expansion of lung cDC numbers that amplifies T cell responses against respiratory viruses.

AB - Protection from infection with respiratory viruses such as influenza A virus (IAV) requires T cell-mediated immune responses initiated by conventional dendritic cells (cDCs) that reside in the respiratory tract. Here, we show that effective induction of T cell responses against IAV in mice requires reinforcement of the resident lung cDC network by cDC progenitors. We found that CCR2-binding chemokines produced during IAV infection recruit pre-cDCs from blood and direct them to foci of infection, increasing the number of progeny cDCs next to sites of viral replication. Ablation of CCR2 in the cDC lineage prevented this increase and resulted in a deficit in IAV-specific T cell responses and diminished resistance to reinfection. These data suggest that the homeostatic network of cDCs in tissues is insufficient for immunity and reveal a chemokine-driven mechanism of expansion of lung cDC numbers that amplifies T cell responses against respiratory viruses.

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SN - 2470-9468

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JO - Science Immunology

JF - Science Immunology

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ER -

Recruitment of dendritic cell progenitors to foci of influenza A virus infection sustains immunity

Abstract

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