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- Title
Subcapsular sinus macrophages maximize germinal center development in non-draining lymph nodes during blood-borne viral infection.
- Authors
Aguilar, Cynthia C.; Kalia, Anurag; Brisse, Morgan E.; Dowd, Kimberly A.; Wise-Dent, Olivia; Burgomaster, Katherine E.; Droppo, Joanna; Pierson, Theodore C.; Hickman, Heather D.
- Abstract
Lymph node (LN) germinal centers (GCs) are critical sites for B cell activation and differentiation. GCs develop after specialized CD169+ macrophages residing in LN sinuses filter antigens (Ags) from the lymph and relay these Ags into proximal B cell follicles. Many viruses, however, first reach LNs through the blood during viremia (virus in the blood), rather than through lymph drainage from infected tissue. How LNs capture viral Ag from the blood to allow GC development is not known. Here, we followed Zika virus (ZIKV) dissemination in mice and subsequent GC formation in both infected tissue–draining and non-draining LNs. From the footpad, ZIKV initially disseminated through two LN chains, infecting LN macrophages and leading to GC formation. Despite rapid ZIKV viremia, non-draining LNs were not infected for several days. Non-draining LN infection correlated with virus-induced vascular leakage and neutralization of permeability reduced LN macrophage attrition. Depletion of non-draining LN macrophages significantly decreased GC B cells in these nodes. Thus, although LNs inefficiently captured viral Ag directly from the blood, GC formation in non-draining LNs proceeded similarly to draining LNs through LN sinus CD169+ macrophages. Together, our findings reveal a conserved pathway allowing LN macrophages to activate antiviral B cells in LNs distal from infected tissue after blood-borne viral infection. Editor summary: Systemic Zika virus (ZIKV) infection induces germinal centers (GCs) in tissue-draining and non-draining lymph nodes (LNs). Viral antigen is captured from the lymphatics and relayed to draining LN follicles by CD169+ subcapsular sinus macrophages (SSMs). However, the pathways by which ZIKV is disseminated from the blood to LNs during blood infection (viremia) are not well understood. Aguilar et al. studied GC formation in non-draining LNs after ZIKV infection in mice. ZIKV-induced vascular leakage resulted in infection of SSMs, which induced delayed GC responses in non-draining LNs. These findings highlight the importance of LN SSMs in promoting humoral immunity during viremia. —Hannah Isles
- Subjects
BLOODBORNE infections; GERMINAL centers; LYMPH nodes; VIRUS diseases; B cell differentiation
- Publication
Science Immunology, 2024, Vol 9, Issue 93, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.adi4926