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dc.contributor.authorHoyt, T. R.
dc.contributor.authorKochetkova, I.
dc.contributor.authorDobrinen, E.
dc.contributor.authorMeissner, Nicole
dc.date.accessioned2015-03-17T15:31:45Z
dc.date.available2015-03-17T15:31:45Z
dc.date.issued2015-02
dc.identifier.citationHoyt, Teri R., Erin Dobrinen, Irina Kochetkova, and Nicole Meissner. B cells modulate systemic responses to Pneumocystis lung infection and protect on-demand hematopoiesis via T cell-independent, innate mechanism when type-I-IFN-signaling is absent. Infection and Immunity. December 2014. Pages 743-758. https://dx.doi.org/10.1128/IAI.02639-14en_US
dc.identifier.issn0019-9567
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/8932
dc.description.abstractHIV infection results in a complex immunodeficiency due to loss of CD4+ T cells, impaired type I interferon (IFN) responses, and B cell dysfunctions causing susceptibility to opportunistic infections such as Pneumocystis murina pneumonia and unexplained comorbidities, including bone marrow dysfunctions. Type I IFNs and B cells critically contribute to immunity to Pneumocystis lung infection. We recently also identified B cells as supporters of on-demand hematopoiesis following Pneumocystis infection that would otherwise be hampered due to systemic immune effects initiated in the context of a defective type I IFN system. While studying the role of type I IFNs in immunity to Pneumocystis infection, we discovered that mice lacking both lymphocytes and type I IFN receptor (IFrag−/−) developed progressive bone marrow failure following infection, while lymphocyte-competent type I IFN receptor-deficient mice (IFNAR−/−) showed transient bone marrow depression and extramedullary hematopoiesis. Lymphocyte reconstitution of lymphocyte-deficient IFrag−/− mice pointed to B cells as a key player in bone marrow protection. Here we define how B cells protect on-demand hematopoiesis following Pneumocystis lung infection in our model. We demonstrate that adoptive transfer of B cells into IFrag−/− mice protects early hematopoietic progenitor activity during systemic responses to Pneumocystis infection, thus promoting replenishment of depleted bone marrow cells. This activity is independent of CD4+ T cell help and B cell receptor specificity and does not require B cell migration to bone marrow. Furthermore, we show that B cells protect on-demand hematopoiesis in part by induction of interleukin-10 (IL-10)- and IL-27-mediated mechanisms. Thus, our data demonstrate an important immune modulatory role of B cells during Pneumocystis lung infection that complement the modulatory role of type I IFNs to prevent systemic complications.en_US
dc.subjectPathologyen_US
dc.subjectMicrobiologyen_US
dc.subjectImmunologyen_US
dc.titleB cells modulate systemic responses to Pneumocystis lung infection and protect on-demand hematopoiesis via T cell-independent, innate mechanism when type-I-IFN-signaling is absenten_US
dc.typeArticleen_US
mus.citation.extentfirstpage743en_US
mus.citation.extentlastpage758en_US
mus.citation.issue2en_US
mus.citation.journaltitleInfection and Immunityen_US
mus.citation.volume83en_US
mus.identifier.categoryHealth & Medical Sciencesen_US
mus.identifier.categoryLife Sciences & Earth Sciencesen_US
mus.identifier.doi10.1128/IAI.02639-14en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.collegeCollege of Agricultureen_US
mus.relation.collegeCollege of Letters & Science
mus.relation.collegeCollege of Agriculture
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US


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