PMID- 26381487
OWN - NLM
STAT- MEDLINE
DCOM- 20160413
LR  - 20220330
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Linking)
VI  - 45
IP  - 12
DP  - 2015 Dec
TI  - A novel experimental model of Cryptococcus neoformans-related immune 
      reconstitution inflammatory syndrome (IRIS) provides insights into pathogenesis.
PG  - 3339-50
LID - 10.1002/eji.201545689 [doi]
AB  - Antiretroviral therapy (ART) has yielded major advances in fighting the HIV 
      pandemic by restoring protective immunity. However, a significant proportion of 
      HIV patients co-infected with the opportunistic fungal pathogen Cryptococcus 
      neoformans paradoxically develops a life-threatening immune reconstitution 
      inflammatory syndrome (IRIS) during antiretroviral therapy. Despite several 
      clinical studies, the underlying pathomecha-nisms are poorly understood. Here, we 
      present the first mouse model of cryptococcal IRIS that allows for a detailed 
      analysis of disease development. Lymphocyte-deficient RAG-1(-/-) mice are 
      infected with C. neoformans and 4 weeks later adoptively transferred with 
      purified CD4(+) T cells. Reconstitution of CD4(+) T cells is sufficient to induce 
      a severe inflammatory disease similar to clinical IRIS in C. neoformans-infected 
      RAG-1(-/-) mice of different genetic backgrounds and immunological phenotypes 
      (i.e. C57BL/6 and BALB/c). Multiorgan inflammation is accompanied by a systemic 
      release of distinct proinflammatory cytokines, i.e. IFN-gamma, IL-6, and TNF-alpha. IRIS 
      development is characterized by infection-dependent activation of donor CD4(+) T 
      cells, which are the source of IFN-gamma. Interestingly, IFN-gamma-mediated effects are 
      not required for disease induction. Taken together, this novel mouse model of 
      cryptococcal IRIS provides a useful tool to verify potential mechanisms of 
      pathogenesis, revealing targets for diagnosis and therapeutic interventions.
CI  - (c) 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Eschke, Maria
AU  - Eschke M
AD  - Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and 
      Biomedicine, College of Veterinary Medicine, University of Leipzig, Leipzig, 
      Germany.
FAU - Piehler, Daniel
AU  - Piehler D
AD  - Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and 
      Biomedicine, College of Veterinary Medicine, University of Leipzig, Leipzig, 
      Germany.
FAU - Schulze, Bianca
AU  - Schulze B
AD  - Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and 
      Biomedicine, College of Veterinary Medicine, University of Leipzig, Leipzig, 
      Germany.
FAU - Richter, Tina
AU  - Richter T
AD  - Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and 
      Biomedicine, College of Veterinary Medicine, University of Leipzig, Leipzig, 
      Germany.
FAU - Grahnert, Andreas
AU  - Grahnert A
AD  - Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and 
      Biomedicine, College of Veterinary Medicine, University of Leipzig, Leipzig, 
      Germany.
FAU - Protschka, Martina
AU  - Protschka M
AD  - Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and 
      Biomedicine, College of Veterinary Medicine, University of Leipzig, Leipzig, 
      Germany.
FAU - Muller, Uwe
AU  - Muller U
AD  - Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and 
      Biomedicine, College of Veterinary Medicine, University of Leipzig, Leipzig, 
      Germany.
FAU - Kohler, Gabriele
AU  - Kohler G
AD  - Institute for Pathology, Klinikum Fulda gAG, Fulda, Germany.
FAU - Hofling, Corinna
AU  - Hofling C
AD  - Paul Flechsig Institute for Brain Research, Faculty of Medicine, University of 
      Leipzig, Leipzig, Germany.
FAU - Rossner, Steffen
AU  - Rossner S
AD  - Paul Flechsig Institute for Brain Research, Faculty of Medicine, University of 
      Leipzig, Leipzig, Germany.
FAU - Alber, Gottfried
AU  - Alber G
AD  - Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and 
      Biomedicine, College of Veterinary Medicine, University of Leipzig, Leipzig, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151012
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Homeodomain Proteins)
RN  - 128559-51-3 (RAG-1 protein)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Cell Movement
MH  - Cryptococcosis/*complications
MH  - *Cryptococcus neoformans
MH  - Disease Models, Animal
MH  - Homeodomain Proteins/physiology
MH  - Immune Reconstitution Inflammatory Syndrome/*etiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
OTO - NOTNLM
OT  - CD4+ T cells
OT  - Cryptococcus neoformans
OT  - Fungal immunity
OT  - Immune reconstitution
OT  - Inflammation
EDAT- 2015/09/19 06:00
MHDA- 2016/04/14 06:00
CRDT- 2015/09/19 06:00
PHST- 2015/03/25 00:00 [received]
PHST- 2015/09/01 00:00 [revised]
PHST- 2015/09/18 00:00 [accepted]
PHST- 2015/09/19 06:00 [entrez]
PHST- 2015/09/19 06:00 [pubmed]
PHST- 2016/04/14 06:00 [medline]
AID - 10.1002/eji.201545689 [doi]
PST - ppublish
SO  - Eur J Immunol. 2015 Dec;45(12):3339-50. doi: 10.1002/eji.201545689. Epub 2015 Oct 
      12.