Pulmonary lymphoid tissue induced after SARS-CoV-2 infection in rhesus macaques

Front Immunol. 2025 Mar 12:16:1533050. doi: 10.3389/fimmu.2025.1533050. eCollection 2025.

Abstract

Introduction: Lung diseases are widespread worldwide. Pulmonary immunity plays a vital role against lung pathogens, including SARS-CoV-2 infection. Understanding the pathogenesis, including the development of local immune responses to infection, is fundamental for developing interventions to control the viral infection.

Methods: Using immunohistochemistry, we investigated the distribution of immune cells in the lungs of rhesus macaques experimentally infected with SARS-CoV-2 and euthanized 11-14 days later.

Results: Tertiary lymphoid tissue was found in all SARS-CoV-2 infected animals. The number (13.9 vs 1.5 iPLT number/ lung cm2), size (25992 vs 13946 µm2) and total area (0.46 vs 0.02 mm2 iPLT/ lung cm2) of the lymphoid tissue aggregations were significantly higher in SARS-CoV-2 infected animals than that of normal controls. This induced pulmonary lymphoid tissues comprised B cells, T cells, CD169 macrophages, and follicular dendritic cells with evidence of lymphocyte priming and differentiation.

Discussion: The results suggest local immunity plays an important role in the SARS-CoV-2 infection. Further study of pulmonary immunity could lead to new interventions to develop vaccine strategies and discover new immune-regulatory biomarkers in monitoring and controlling SARS-CoV-2 infection and other lung diseases.

Keywords: CD169; SAR-CoV-2; animal model; immune response; pulmonary mucosa associated lymphoid tissue; respiratory viral infection.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • COVID-19* / immunology
  • COVID-19* / pathology
  • Disease Models, Animal
  • Lung* / immunology
  • Lung* / pathology
  • Lung* / virology
  • Lymphoid Tissue* / immunology
  • Lymphoid Tissue* / pathology
  • Lymphoid Tissue* / virology
  • Macaca mulatta
  • Macrophages / immunology
  • Male
  • SARS-CoV-2* / immunology
  • T-Lymphocytes / immunology

Grants and funding

The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by internal seed grants to the California National Primate Research Center and the Center for Immunology and Infectious Diseases, R21 AI143454-02S1 (S.S.I.), and the California National Primate Research Center base grant P51OD011107.