Generation of plasma cells and CD27 - IgD - B cells during hantavirus infection is associated with distinct pathological findings

Autor: Mirjam Dannborg, Clas Ahlm, Gleyder Roman-Sosa, Pauline Ocaya, Julia Wigren Byström, Andrea Puhar, Johanna Tauriainen, Christopher Sundling, Rohit K. Jangra, Kimia T Maleki, Félix A. Rey, Mattias Forsell, Pablo Guardado-Calvo, Therese Thunberg, Eva Mittler, Andy Dernstedt, Jonas Klingström, Anne Tuiskunen-Bäck, Kartik Chandran, Priscilla F Kerkman, Lalitha Tadala
Přispěvatelé: Umeå Centre for Microbial Research (UCMR), Umeå University, Albert Einstein College of Medicine [New York], Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the following grants: Intramural funds (AN 2.2.1.2-76-14) and Biotechnology grant (2.1.12-128714) from the Medical Faculty, Umeå University, and funds from the Swedish Society of Medicine (SLS-787091) to MF, research grants from the Västerbotten County Council (VLL-579011 and VLL-850681) to MF and CA, the Swedish Foundation for Strategic Research to CA and JK, the Knut and Alice Wallenberg Foundation (KAW 2015.0225) and Centre for Microbial Research (UCMR) and The Laboratory for Molecular Infection Medicine Sweden (MIMS) to AP, National Institutes of Health R01AI132633 to KC, the Swedish Science Council (2018-02646_3) and intramural funds from the Karolinska Institutet to JK., Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Clinical & Translational Immunology
Clinical & Translational Immunology, 2021, 10, pp.e1313. ⟨10.1002/cti2.1313⟩
Clinical & Translational Immunology, Wiley, 2021, 10, pp.e1313. ⟨10.1002/cti2.1313⟩
Clinical & Translational Immunology, Vol 10, Iss 7, Pp n/a-n/a (2021)
ISSN: 2050-0068
Popis: International audience; Objective : Human hantavirus infections can cause haemorrhagic fever with renal syndrome (HFRS). The pathogenic mechanisms are not fully understood, nor if they affect the humoral immune system. The objective of this study was to investigate humoral immune responses to hantavirus infection and to correlate them to the typical features of HFRS: thrombocytopenia and transient kidney dysfunction.Methods : We performed a comprehensive characterisation of longitudinal antiviral B-cell responses of 26 hantavirus patients and combined this with paired clinical data. In addition, we measured extracellular adenosine triphosphate (ATP) and its breakdown products in circulation and performed in vitro stimulations to address its effect on B cells.Results : We found that thrombocytopenia was correlated to an elevated frequency of plasmablasts in circulation. In contrast, kidney dysfunction was indicative of an accumulation of CD27−IgD− B cells and CD27−/low plasmablasts. Finally, we provide evidence that high levels of extracellular ATP and matrix metalloproteinase 8 can contribute to shedding of CD27 during human hantavirus infection.Conclusion : Our findings demonstrate that thrombocytopenia and kidney dysfunction associate with distinctly different effects on the humoral immune system. Moreover, hantavirus-infected individuals have significantly elevated levels of extracellular ATP in circulation.
Databáze: OpenAIRE
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