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Phenotypic and functional analysis of CD1a+ dendritic cells from cats chronically infected with feline
Lin Zhang1, Stacie Reckling2, Gregg A Dean1
1Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USA.
Insights
Feline immunodeficiency virus (FIV) infection impairs dendritic cell (DC) migration and antigen presentation in cats, a model for HIV-1. Resident DCs remain functional, suggesting localized immune dysregulation.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Dendritic cell (DC) dysfunction is implicated in HIV-1 pathogenesis.
- In vivo studies assessing DC function during retroviral infection are limited.
Purpose of the Study:
- To investigate the in vivo and in vitro maturation and function of dendritic cells (DCs) during feline immunodeficiency virus (FIV) infection in cats.
- To utilize the FIV-cat model to understand DC behavior relevant to HIV-1 infection.
Main Methods:
- Comparison of CD1a+ DC migration, surface phenotype, endocytosis, mixed leukocyte reaction (MLR), and regulatory T cell (Treg) induction.
- Isolation of CD1a+ cells from lymph nodes of FIV-infected and control cats.
- In vivo and in vitro assessments of DC function.
Main Results:
- Resident CD1a+ DCs in lymph nodes of chronically FIV-infected cats exhibited mature phenotypes.
- These resident DCs maintained the ability to stimulate T cell proliferation and override Treg suppression.
- FIV infection negatively impacted the antigen presentation and migratory capabilities of CD1a+ cells in tissues.
Conclusions:
- While resident lymph node DCs retain function, FIV infection compromises critical DC functions like migration and antigen presentation.
- These findings highlight localized immune dysregulation in FIV infection, offering insights into HIV-1 pathogenesis.
Abstract:
Numerous studies suggest dendritic cell (DC) dysfunction is central to the dysregulated immune response during HIV infection; however, in vivo studies are lacking. In the present study we used feline immunodeficiency virus (FIV) infection of cats as a model for HIV-1 infection to assess the maturation and function of dendritic cells, in vivo and in vitro. We compared CD1a+ DC migration, surface phenotype, endocytosis, mixed leukocyte reaction (MLR) and regulatory T cell (Treg) phenotype induction by CD1a+ cells isolated from lymph nodes of FIV-infected and control cats. Results showed that resident CD1a+ DC in lymph nodes of chronically FIV-infected cats are phenotypically mature, can stimulate normal primary T cell proliferation, override Treg suppression and do not skew toward Treg induction. In contrast, FIV infection had deleterious effects on antigen presentation and migratory capacity of CD1a+ cells in tissues.
