Poster Presentation 14th Lorne Infection and Immunity 2024

Differential kinetics of splenic CD169+ macrophage death is one underlying cause of virus infection fate regulation (#123)

Valentina Casella 1 2 , Eva Domenjo-Vila 2 , Anna Esteve-Codina 3 , Mireia Pedragosa 1 , Paula Cebollada Rica 2 , Enric Vidal 4 5 , Iván de la Rubia 1 6 , Cristina López-Rodríguez 7 , Gennady Bocharov 8 9 , Jordi Argilaguet 2 4 5 , Andreas Meyerhans 2 10
  1. Universitat Pompeu Fabra, Barcelona, SPAIN, Spain
  2. Infection Biology Laboratory, Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra (UPF), Barcelona, Spain
  3. CNAG-CRG Centre for Genomic Regulation (CRG), Barcelona, Spain
  4. Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Bellaterra, Spain
  5. IRTA, Programa de Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Bellaterra, Spain
  6. EMBL Australia Partner Laboratory Network at the Australian National University, Acton, Australia
  7. Immunology Unit, Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra (UPF), Barcelona, Spain
  8. Marchuk Institute of Numerical Mathematics, Russian Academy of Sciences, Moskow, Russia
  9. Sechenov First Moskow State Medical University, Moskow, Russia
  10. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain, SPAIN

Acute infection and chronic infection are the two most common fates of pathogenic virus infections. While several factors that contribute to these fates are described, the critical control points and the mechanisms that underlie infection fate regulation are incompletely understood. Using the acute and chronic lymphocytic choriomeningitis virus (LCMV) infection model of mice, we find that the early dynamic pattern of the IFN-I response is a differentiating trait between both infection fates. Acute-infected mice generate a 2-wave IFN-I response while chronic-infected mice generate only a 1-wave response. The underlying cause is a temporal difference in CD8 T cell-mediated killing of splenic marginal zone CD169+ macrophages. It occurs later in acute infection and thus enables CD169+ marginal zone macrophages to produce the 2nd IFN-I wave. This is required for subsequent immune events including induction of inflammatory macrophages, generation of effector CD8+ T cells and virus clearance. Importantly, these benefits come at a cost for the host in the form of spleen fibrosis. Due to an earlier marginal zone destruction, these ordered immune events are deregulated in chronic infection. Our findings demonstrate the critical importance of kinetically well-coordinated sequential immune events for acute infection control and highlights that it may come at a cost for the host organism.

  1. Casella V, Domenjo-Vila E, Esteve-Codina A, Pedragosa M, Cebollada Rica P, Vidal E, de la Rubia I, López-Rodríguez C, Bocharov G, Argilaguet J, Meyerhans A. Differential kinetics of splenic CD169+ macrophage death is one underlying cause of virus infection fate regulation. Cell Death Dis. 2023 Dec 18;14(12):838. doi: 10.1038/s41419-023-06374-y. PMID: 38110339; PMCID: PMC10728219.