Johan Rasmuson1, Jamshid Pourazar2, Mats Linderholm3, Thomas Sandström2, Anders Blomberg2, Clas Ahlm3. 1. Infectious Diseases, Department of Clinical Microbiology, Umeå University, Umeå, Sweden. Electronic address: johan.rasmuson@climi.umu.se. 2. Respiratory Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. 3. Infectious Diseases, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
Abstract
BACKGROUND: Hantaviruses cause two clinical syndromes: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The clinical spectrum in HFRS also often involves respiratory symptoms. As information about the pulmonary pathogenesis in HFRS is limited, we aimed to further study the local airway immune response in the lower airways. METHODS: Bronchoscopy was performed in 15 hospitalized patients with HFRS, with sampling of endobronchial mucosal biopsies and BAL fluid. Biopsies were stained for leukocytes, lymphocyte subsets, and vascular endothelial adhesion molecules. BAL fluid and blood lymphocyte subsets were determined using flow cytometry. Fourteen healthy volunteers acted as a control group. RESULTS: Compared with control subjects, endobronchial mucosal biopsies from patients with HFRS revealed increased numbers of CD8(+) T cells in both epithelium and submucosa (P ≤ .001), along with an increase in submucosal CD4(+) T cells (P = .001). In contrast, patients' submucosal neutrophil and eosinophil numbers were reduced (P < .001). The expression of vascular cell adhesion molecule-1 (VCAM-1) was enhanced in patients with HFRS (P < .001). In patients with HFRS, analyses of T-cell subsets in BAL fluid showed higher proportions of CD3(+) and CD8(+) T cells (P = .011 and P = .025) and natural killer cells (P < .001), together with an increased expression of activation markers human leukocyte antigen-DR (HLA-DR) and CD25 on T cells (P < .001 and P < .001). CONCLUSIONS: The present findings indicate a local immune response in terms of activated T lymphocytes in the lungs of patients with HFRS. The elevated expression of activation markers and VCAM-1 further implies the importance of cytotoxic lymphocytes in the pathogenesis of pulmonary involvement in HFRS.
BACKGROUND: Hantaviruses cause two clinical syndromes: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The clinical spectrum in HFRS also often involves respiratory symptoms. As information about the pulmonary pathogenesis in HFRS is limited, we aimed to further study the local airway immune response in the lower airways. METHODS: Bronchoscopy was performed in 15 hospitalized patients with HFRS, with sampling of endobronchial mucosal biopsies and BAL fluid. Biopsies were stained for leukocytes, lymphocyte subsets, and vascular endothelial adhesion molecules. BAL fluid and blood lymphocyte subsets were determined using flow cytometry. Fourteen healthy volunteers acted as a control group. RESULTS: Compared with control subjects, endobronchial mucosal biopsies from patients with HFRS revealed increased numbers of CD8(+) T cells in both epithelium and submucosa (P ≤ .001), along with an increase in submucosal CD4(+) T cells (P = .001). In contrast, patients' submucosal neutrophil and eosinophil numbers were reduced (P < .001). The expression of vascular cell adhesion molecule-1 (VCAM-1) was enhanced in patients with HFRS (P < .001). In patients with HFRS, analyses of T-cell subsets in BAL fluid showed higher proportions of CD3(+) and CD8(+) T cells (P = .011 and P = .025) and natural killer cells (P < .001), together with an increased expression of activation markers human leukocyte antigen-DR (HLA-DR) and CD25 on T cells (P < .001 and P < .001). CONCLUSIONS: The present findings indicate a local immune response in terms of activated T lymphocytes in the lungs of patients with HFRS. The elevated expression of activation markers and VCAM-1 further implies the importance of cytotoxic lymphocytes in the pathogenesis of pulmonary involvement in HFRS.
Authors: Antti Vaheri; Tomas Strandin; Jussi Hepojoki; Tarja Sironen; Heikki Henttonen; Satu Mäkelä; Jukka Mustonen Journal: Nat Rev Microbiol Date: 2013-08 Impact factor: 60.633
Authors: Kimia T Maleki; Johanna Tauriainen; Marina García; Priscilla F Kerkman; Wanda Christ; Joana Dias; Julia Wigren Byström; Edwin Leeansyah; Mattias N Forsell; Hans-Gustaf Ljunggren; Clas Ahlm; Niklas K Björkström; Johan K Sandberg; Jonas Klingström Journal: Cell Rep Med Date: 2021-03-16