PMID- 31126019
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220310
IS  - 2309-608X (Electronic)
IS  - 2309-608X (Linking)
VI  - 5
IP  - 2
DP  - 2019 May 23
TI  - HIV-Associated Cryptococcal Immune Reconstitution Inflammatory Syndrome Is 
      Associated with Aberrant T Cell Function and Increased Cytokine Responses.
LID - 10.3390/jof5020042 [doi]
LID - 42
AB  - Cryptococcal meningitis remains a significant opportunistic infection among 
      HIV-infected patients, contributing 15-20% of HIV-related mortality. A 
      complication of initiating antiretroviral therapy (ART) following opportunistic 
      infection is immune reconstitution inflammatory syndrome (IRIS). IRIS afflicts 
      10-30% of HIV-infected patients with cryptococcal meningitis (CM), but its 
      immunopathogenesis is poorly understood. We compared circulating T cell memory 
      subsets and cytokine responses among 17 HIV-infected Ugandans with CM: 11 with 
      and 6 without CM-IRIS. At meningitis diagnosis, stimulation with cryptococcal 
      capsule component, glucuronoxylomannan (GXM) elicited consistently lower 
      frequencies of CD4(+) and CD8(+) T cell memory subsets expressing intracellular 
      cytokines (IL-2, IFN-gamma, and IL-17) among subjects who subsequently developed 
      CM-IRIS. After ART initiation, T cells evolved to show a decreased CD8(+) central 
      memory phenotype. At the onset of CM-IRIS, stimulation more frequently generated 
      polyfunctional IL-2(+)/IL-17(+) CD4(+) T cells in patients with CM-IRIS. 
      Moreover, CD8(+) central and effector memory T cells from CM-IRIS subjects also 
      demonstrated more robust IL-2 responses to antigenic stimulation vs. controls. 
      Thus, ART during CM elicits distinct differences in T cell cytokine production in 
      response to cryptococcal antigens both prior to and during the development of 
      IRIS, suggesting an immunologic foundation for the development of this morbid 
      complication of CM infection.
FAU - Meya, David B
AU  - Meya DB
AUID- ORCID: 0000-0002-4138-240X
AD  - Infectious Diseases Institute, Makerere University, Kampala P.O. Box 22418, 
      Uganda. david.meya@gmail.com.
AD  - Department of Medicine, Center for Infectious Diseases and Microbiology 
      Translational Research, University of Minnesota, Minneapolis, MN 55455, USA. 
      david.meya@gmail.com.
AD  - School of Medicine, College of Health Sciences, Makerere University, Kampala P.O. 
      Box 7072, Uganda. david.meya@gmail.com.
FAU - Okurut, Samuel
AU  - Okurut S
AUID- ORCID: 0000-0002-9292-8687
AD  - Infectious Diseases Institute, Makerere University, Kampala P.O. Box 22418, 
      Uganda. okuruts@gmail.com.
FAU - Zziwa, Godfrey
AU  - Zziwa G
AD  - Research Department, Makerere University Walter Reed Project, Plot 42, Nakasero 
      Road, Kampala P.O. Box 1624, Uganda. gzziwa@muwrp.org.
FAU - Cose, Stephen
AU  - Cose S
AUID- ORCID: 0000-0002-5156-037X
AD  - Clinical Research Department, London School of Hygiene & Tropical Medicine, 
      Keppel Street, London WC1E 7HT, UK. stephen.cose@mrcuganda.org.
AD  - MRC/UVRI and LSHTM Uganda Research Unit, Plot 51-59 Nakiwogo Road, Entebbe 
      P.O.Box 49, Uganda. stephen.cose@mrcuganda.org.
FAU - Boulware, David R
AU  - Boulware DR
AUID- ORCID: 0000-0002-4715-0060
AD  - Department of Medicine, Center for Infectious Diseases and Microbiology 
      Translational Research, University of Minnesota, Minneapolis, MN 55455, USA. 
      boulw001@umn.edu.
FAU - Janoff, Edward N
AU  - Janoff EN
AUID- ORCID: 0000-0003-2702-5729
AD  - Mucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado, 
      Denver, Aurora, CO 80045, USA. Edward.Janoff@ucdenver.edu.
LA  - eng
GR  - MR/M007413/1/MRC_/Medical Research Council/United Kingdom
GR  - MR/S004963/1/MRC_/Medical Research Council/United Kingdom
GR  - R01AI078934, U01AI089244, R01AI108479/NH/NIH HHS/United States
GR  - 107742/Z/15/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
DEP - 20190523
PL  - Switzerland
TA  - J Fungi (Basel)
JT  - Journal of fungi (Basel, Switzerland)
JID - 101671827
PMC - PMC6616503
OTO - NOTNLM
OT  - CD4 T cells
OT  - CD8 T cells
OT  - Cryptococcus
OT  - HIV
OT  - IRIS
OT  - adaptive immune response
OT  - cryptococcal meningitis
COIS- The authors declare no conflict of interest.
EDAT- 2019/05/28 06:00
MHDA- 2019/05/28 06:01
PMCR- 2019/05/23
CRDT- 2019/05/26 06:00
PHST- 2019/04/05 00:00 [received]
PHST- 2019/04/24 00:00 [revised]
PHST- 2019/04/29 00:00 [accepted]
PHST- 2019/05/26 06:00 [entrez]
PHST- 2019/05/28 06:00 [pubmed]
PHST- 2019/05/28 06:01 [medline]
PHST- 2019/05/23 00:00 [pmc-release]
AID - jof5020042 [pii]
AID - jof-05-00042 [pii]
AID - 10.3390/jof5020042 [doi]
PST - epublish
SO  - J Fungi (Basel). 2019 May 23;5(2):42. doi: 10.3390/jof5020042.