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- Title
Recruitment of dendritic cell progenitors to foci of influenza A virus infection sustains immunity.
- Authors
Cabeza-Cabrerizo, Mar; Minutti, Carlos M.; da Costa, Mariana Pereira; Cardoso, Ana; Jenkins, Robert P.; Kulikauskaite, Justina; Buck, Michael D.; Piot, Cécile; Rogers, Neil; Crotta, Stefania; Whittaker, Lynne; Encabo, Hector Huerga; McCauley, John W.; Allen, Judith E.; Pasparakis, Manolis; Wack, Andreas; Sahai, Erik; Reis e Sousa, Caetano
- Abstract
Infected lungs call for dendritic cell backup: Resident dendritic cells (DCs) within the lung epithelium are positioned to rapidly detect invading pathogens and initiate an adaptive immune response but can be expanded through recruitment of blood-derived progenitors. In a mouse model of influenza virus infection, Cabeza-Cabrerizo et al. show that expression of the chemokine receptor CCR2 is required for recruitment of DC progenitors (pre-DCs) to the lungs and subsequent positioning at foci of infection. Using mice with conditional deletion of CCR2 in the DC lineage, they found that pre-DC recruitment is necessary for effective T cell responses and protection against reinfection. These results demonstrate that expansion of the homeostatic lung DC network by circulating pre-DCs is essential for immunity against respiratory viruses. 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.
- Subjects
VIRUS diseases; INFLUENZA A virus; DENDRITIC cells; INFLUENZA viruses; PROGENITOR cells
- Publication
Science Immunology, 2021, Vol 6, Issue 65, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.abi9331