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Alterations in germinal center formation and B cell activation during severe Orientia tsutsugamushi infection in mice.
- Source :
- PLoS Neglected Tropical Diseases, Vol 17, Iss 5, p e0011090 (2023)
- Publication Year :
- 2023
- Publisher :
- Public Library of Science (PLoS), 2023.
-
Abstract
- Scrub typhus is a poorly studied but life-threatening disease caused by the intracellular bacterium Orientia tsutsugamushi (Ot). Cellular and humoral immunity in Ot-infected patients is not long-lasting, waning as early as one-year post-infection; however, its underlying mechanisms remain unclear. To date, no studies have examined germinal center (GC) or B cell responses in Ot-infected humans or experimental animals. This study was aimed at evaluating humoral immune responses at acute stages of severe Ot infection and possible mechanisms underlying B cell dysfunction. Following inoculation with Ot Karp, a clinically dominant strain known to cause lethal infection in C57BL/6 mice, we measured antigen-specific antibody titers, revealing IgG2c as the dominant isotype induced by infection. Splenic GC responses were evaluated by immunohistology, co-staining for B cells (B220), T cells (CD3), and GCs (GL-7). Organized GCs were evident at day 4 post-infection (D4), but they were nearly absent at D8, accompanied by scattered T cells throughout splenic tissues. Flow cytometry revealed comparable numbers of GC B cells and T follicular helper (Tfh) cells at D4 and D8, indicating that GC collapse was not due to excessive death of these cell subtypes at D8. B cell RNAseq analysis revealed significant differences in expression of genes associated with B cell adhesion and co-stimulation at D8 versus D4. The significant downregulation of S1PR2 (a GC-specific adhesion gene) was most evident at D8, correlating with disrupted GC formation. Signaling pathway analysis uncovered downregulation of 71% of B cell activation genes at D8, suggesting attenuation of B cell activation during severe infection. This is the first study showing the disruption of B/T cell microenvironment and dysregulation of B cell responses during Ot infection, which may help understand the transient immunity associated with scrub typhus.
- Subjects :
- Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Subjects
Details
- Language :
- English
- ISSN :
- 19352727 and 19352735
- Volume :
- 17
- Issue :
- 5
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS Neglected Tropical Diseases
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.0df32209f6704d04a437cd9b9f2eb77e
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.pntd.0011090