Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection

J. Rasmuson, J. Pourazar, N. Mohamed, K. Lejon, M. Evander, A. Blomberg, C. Ahlm

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Abstract

Hantavirus infections may cause severe and sometime life-threatening lung failure. The pathogenesis is not fully known and there is an urgent need for effective treatment. We aimed to investigate the association between pulmonary viral load and immune responses, and their relation to disease severity. Bronchoscopy with sampling of bronchoalveolar lavage (BAL) fluid was performed in 17 patients with acute Puumala hantavirus infection and 16 healthy volunteers acting as controls. Lymphocyte subsets, granzyme concentrations, and viral load were determined by flow cytometry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Analyses of BAL fluid revealed significantly higher numbers of activated CD8+ T cells and natural killer (NK) cells, as well as higher concentrations of the cytotoxins granzymes A and B in hantavirus-infected patients, compared to controls. In patients, Puumala hantavirus RNA was detected in 88 % of BAL cell samples and correlated inversely to the T cell response. The magnitude of the pulmonary cytotoxic lymphocyte response correlated to the severity of disease and systemic organ dysfunction, in terms of need for supplemental oxygen treatment, hypotension, and laboratory data indicating renal failure, cardiac dysfunction, vascular leakage, and cell damage. Regulatory T cell numbers were significantly lower in patients compared to controls, and may reflect inadequate immune regulation during hantavirus infection. Hantavirus infection elicits a pronounced cytotoxic lymphocyte response in the lungs. The magnitude of the immune response was associated with disease severity. These results give insights into the pathogenesis and possibilities for new treatments.

Original languageEnglish
Pages (from-to)713-721
Number of pages9
JournalEuropean Journal of Clinical Microbiology and Infectious Diseases
Volume35
Issue number4
DOIs
Publication statusPublished - 1 Apr 2016

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Hantavirus Infections
Granzymes
Hantavirus
Lung
Bronchoalveolar Lavage Fluid
Viral Load
Lymphocytes
T-Lymphocytes
Lymphocyte Subsets
Cytotoxins
Bronchoscopy
Bronchoalveolar Lavage
Regulatory T-Lymphocytes
Natural Killer Cells
Hypotension
Reverse Transcription
Renal Insufficiency
Blood Vessels
Healthy Volunteers
Flow Cytometry

Cite this

Rasmuson, J. ; Pourazar, J. ; Mohamed, N. ; Lejon, K. ; Evander, M. ; Blomberg, A. ; Ahlm, C. / Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection. In: European Journal of Clinical Microbiology and Infectious Diseases. 2016 ; Vol. 35, No. 4. pp. 713-721.
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Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection. / Rasmuson, J.; Pourazar, J.; Mohamed, N.; Lejon, K.; Evander, M.; Blomberg, A.; Ahlm, C.

In: European Journal of Clinical Microbiology and Infectious Diseases, Vol. 35, No. 4, 01.04.2016, p. 713-721.

Research output: Contribution to journalArticleResearchpeer-review

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