IFN-γ at the site of infection determines rate of clearance of infection in cryptococcal meningitis

In animal models, immunity to cryptococcal infection, as in many chronic fungal and bacterial infections, is associated with a granulomatous inflammatory response, intact cell-mediated immunity, and a Th1 pattern of cytokine release. To examine the correlates of human immunity to cryptococcal infect...

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Main Authors: Asna A. Siddiqui, Annemarie E. Brouwer, Vannaporn Wuthiekanun, Shabbar Jaffar, Robin Shattock, Diane Irving, Joanna Sheldon, Wirongrong Chierakul, Sharon Peacock, Nicholas Day, Nicholas J. White, Thomas S. Harrison
Other Authors: St George's University of London
Format: Article
Published: 2018
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/16609
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spelling th-mahidol.166092018-06-21T15:17:00Z IFN-γ at the site of infection determines rate of clearance of infection in cryptococcal meningitis Asna A. Siddiqui Annemarie E. Brouwer Vannaporn Wuthiekanun Shabbar Jaffar Robin Shattock Diane Irving Joanna Sheldon Wirongrong Chierakul Sharon Peacock Nicholas Day Nicholas J. White Thomas S. Harrison St George's University of London Mahidol University Radboud University Nijmegen Medical Centre London School of Hygiene & Tropical Medicine Nuffield Department of Clinical Medicine Immunology and Microbiology In animal models, immunity to cryptococcal infection, as in many chronic fungal and bacterial infections, is associated with a granulomatous inflammatory response, intact cell-mediated immunity, and a Th1 pattern of cytokine release. To examine the correlates of human immunity to cryptococcal infection in vivo, we analyzed immune parameters at the site of infection over time and assessed the rate of clearance of infection by serial quantitative cerebrospinal fluid (CSF) fungal cultures in 62 patients in a trial of antifungal therapy for HIV-associated cryptococcal meningitis. CSF IL-6, IFN-γ, TNF-α, and IL-8 were significantly higher in survivors compared with nonsurvivors. There were negative correlations between log TNF-α, IFN-γ, and IL-6 levels and baseline cryptococcal CFU. Log IFN-γ, G-CSF, TNF-α, and IL-6 were correlated positively with the rate of fall in log CFU/ml CSF/day. In a linear regression model including antifungal treatment group, baseline CFU, and these cytokines, only treatment group and log IFN-γ remained independently associated with rate of clearance of infection. The results provide direct in vivo evidence for the importance of quantitative differences in IFN-γ secretion in human immune control of granulomatous infections, and increase the rationale for adjunctive IFN-γ in the treatment of refractory HIV-associated cryptococcosis. 2018-06-21T08:17:00Z 2018-06-21T08:17:00Z 2005-02-01 Article Journal of Immunology. Vol.174, No.3 (2005), 1746-1750 00221767 2-s2.0-19944432138 https://repository.li.mahidol.ac.th/handle/123456789/16609 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=19944432138&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Immunology and Microbiology
spellingShingle Immunology and Microbiology
Asna A. Siddiqui
Annemarie E. Brouwer
Vannaporn Wuthiekanun
Shabbar Jaffar
Robin Shattock
Diane Irving
Joanna Sheldon
Wirongrong Chierakul
Sharon Peacock
Nicholas Day
Nicholas J. White
Thomas S. Harrison
IFN-γ at the site of infection determines rate of clearance of infection in cryptococcal meningitis
description In animal models, immunity to cryptococcal infection, as in many chronic fungal and bacterial infections, is associated with a granulomatous inflammatory response, intact cell-mediated immunity, and a Th1 pattern of cytokine release. To examine the correlates of human immunity to cryptococcal infection in vivo, we analyzed immune parameters at the site of infection over time and assessed the rate of clearance of infection by serial quantitative cerebrospinal fluid (CSF) fungal cultures in 62 patients in a trial of antifungal therapy for HIV-associated cryptococcal meningitis. CSF IL-6, IFN-γ, TNF-α, and IL-8 were significantly higher in survivors compared with nonsurvivors. There were negative correlations between log TNF-α, IFN-γ, and IL-6 levels and baseline cryptococcal CFU. Log IFN-γ, G-CSF, TNF-α, and IL-6 were correlated positively with the rate of fall in log CFU/ml CSF/day. In a linear regression model including antifungal treatment group, baseline CFU, and these cytokines, only treatment group and log IFN-γ remained independently associated with rate of clearance of infection. The results provide direct in vivo evidence for the importance of quantitative differences in IFN-γ secretion in human immune control of granulomatous infections, and increase the rationale for adjunctive IFN-γ in the treatment of refractory HIV-associated cryptococcosis.
author2 St George's University of London
author_facet St George's University of London
Asna A. Siddiqui
Annemarie E. Brouwer
Vannaporn Wuthiekanun
Shabbar Jaffar
Robin Shattock
Diane Irving
Joanna Sheldon
Wirongrong Chierakul
Sharon Peacock
Nicholas Day
Nicholas J. White
Thomas S. Harrison
format Article
author Asna A. Siddiqui
Annemarie E. Brouwer
Vannaporn Wuthiekanun
Shabbar Jaffar
Robin Shattock
Diane Irving
Joanna Sheldon
Wirongrong Chierakul
Sharon Peacock
Nicholas Day
Nicholas J. White
Thomas S. Harrison
author_sort Asna A. Siddiqui
title IFN-γ at the site of infection determines rate of clearance of infection in cryptococcal meningitis
title_short IFN-γ at the site of infection determines rate of clearance of infection in cryptococcal meningitis
title_full IFN-γ at the site of infection determines rate of clearance of infection in cryptococcal meningitis
title_fullStr IFN-γ at the site of infection determines rate of clearance of infection in cryptococcal meningitis
title_full_unstemmed IFN-γ at the site of infection determines rate of clearance of infection in cryptococcal meningitis
title_sort ifn-γ at the site of infection determines rate of clearance of infection in cryptococcal meningitis
publishDate 2018
url https://repository.li.mahidol.ac.th/handle/123456789/16609
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