Protection from direct cerebral Cryptococcus infection by interferon-γ-dependent activation of microglial cells

Qing Zhou, Ruth A. Gault, Thomas R. Kozel, William J Murphy

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The brain represents a significant barrier for protective immune responses in both infections disease and cancer. We have recently demonstrated that immunotherapy with anti-CD40 and IL-2 can protect mice against disseminated Cryptococcus infection. We now applied this immunotherapy using a direct cerebral cryptococcosis model to study direct effects in the brain. Administration of anti-CD40 and IL-2 significantly prolonged the survival time of mice infected intracerebrally with Cryptococcus neoformans. The protection was correlated with activation of microglial cells indicated by the up-regulation of MHC II expression on brain CD45lowCD11b+ cells. CD4+ T cells were not required for either the microglial cell activation or anticryptococcal efficacy induced by this immunotherapy. Experiments with IFN-γ knockout mice and IFN-γR knockout mice demonstrated that IFN-γ was critical for both microglial cell activation and the anticryptococcal efficacy induced by anti-CD40/IL-2. Interestingly, while peripheral IFN-γ production and microglial cell activation were observed early after treatment, negligible IFN-γ was detected locally in the brain. These studies indicate that immunotherapy using anti-CD40 and IL-2 can augment host immunity directly in the brain against C. neoformans infection and that IFN-γ is essential for this effect.

Original languageEnglish (US)
Pages (from-to)5753-5761
Number of pages9
JournalJournal of Immunology
Volume178
Issue number9
StatePublished - May 1 2007
Externally publishedYes

Fingerprint

Cryptococcus
Interferons
Immunotherapy
Interleukin-2
Brain
Infection
Cryptococcus neoformans
Knockout Mice
Cryptococcal Meningitis
Immunity
Up-Regulation
T-Lymphocytes
Neoplasms

ASJC Scopus subject areas

  • Immunology

Cite this

Protection from direct cerebral Cryptococcus infection by interferon-γ-dependent activation of microglial cells. / Zhou, Qing; Gault, Ruth A.; Kozel, Thomas R.; Murphy, William J.

In: Journal of Immunology, Vol. 178, No. 9, 01.05.2007, p. 5753-5761.

Research output: Contribution to journalArticle

@article{0ea637e87b3a4107a2df8a9f9d957cd4,
title = "Protection from direct cerebral Cryptococcus infection by interferon-γ-dependent activation of microglial cells",
abstract = "The brain represents a significant barrier for protective immune responses in both infections disease and cancer. We have recently demonstrated that immunotherapy with anti-CD40 and IL-2 can protect mice against disseminated Cryptococcus infection. We now applied this immunotherapy using a direct cerebral cryptococcosis model to study direct effects in the brain. Administration of anti-CD40 and IL-2 significantly prolonged the survival time of mice infected intracerebrally with Cryptococcus neoformans. The protection was correlated with activation of microglial cells indicated by the up-regulation of MHC II expression on brain CD45lowCD11b+ cells. CD4+ T cells were not required for either the microglial cell activation or anticryptococcal efficacy induced by this immunotherapy. Experiments with IFN-γ knockout mice and IFN-γR knockout mice demonstrated that IFN-γ was critical for both microglial cell activation and the anticryptococcal efficacy induced by anti-CD40/IL-2. Interestingly, while peripheral IFN-γ production and microglial cell activation were observed early after treatment, negligible IFN-γ was detected locally in the brain. These studies indicate that immunotherapy using anti-CD40 and IL-2 can augment host immunity directly in the brain against C. neoformans infection and that IFN-γ is essential for this effect.",
author = "Qing Zhou and Gault, {Ruth A.} and Kozel, {Thomas R.} and Murphy, {William J}",
year = "2007",
month = "5",
day = "1",
language = "English (US)",
volume = "178",
pages = "5753--5761",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

TY - JOUR

T1 - Protection from direct cerebral Cryptococcus infection by interferon-γ-dependent activation of microglial cells

AU - Zhou, Qing

AU - Gault, Ruth A.

AU - Kozel, Thomas R.

AU - Murphy, William J

PY - 2007/5/1

Y1 - 2007/5/1

N2 - The brain represents a significant barrier for protective immune responses in both infections disease and cancer. We have recently demonstrated that immunotherapy with anti-CD40 and IL-2 can protect mice against disseminated Cryptococcus infection. We now applied this immunotherapy using a direct cerebral cryptococcosis model to study direct effects in the brain. Administration of anti-CD40 and IL-2 significantly prolonged the survival time of mice infected intracerebrally with Cryptococcus neoformans. The protection was correlated with activation of microglial cells indicated by the up-regulation of MHC II expression on brain CD45lowCD11b+ cells. CD4+ T cells were not required for either the microglial cell activation or anticryptococcal efficacy induced by this immunotherapy. Experiments with IFN-γ knockout mice and IFN-γR knockout mice demonstrated that IFN-γ was critical for both microglial cell activation and the anticryptococcal efficacy induced by anti-CD40/IL-2. Interestingly, while peripheral IFN-γ production and microglial cell activation were observed early after treatment, negligible IFN-γ was detected locally in the brain. These studies indicate that immunotherapy using anti-CD40 and IL-2 can augment host immunity directly in the brain against C. neoformans infection and that IFN-γ is essential for this effect.

AB - The brain represents a significant barrier for protective immune responses in both infections disease and cancer. We have recently demonstrated that immunotherapy with anti-CD40 and IL-2 can protect mice against disseminated Cryptococcus infection. We now applied this immunotherapy using a direct cerebral cryptococcosis model to study direct effects in the brain. Administration of anti-CD40 and IL-2 significantly prolonged the survival time of mice infected intracerebrally with Cryptococcus neoformans. The protection was correlated with activation of microglial cells indicated by the up-regulation of MHC II expression on brain CD45lowCD11b+ cells. CD4+ T cells were not required for either the microglial cell activation or anticryptococcal efficacy induced by this immunotherapy. Experiments with IFN-γ knockout mice and IFN-γR knockout mice demonstrated that IFN-γ was critical for both microglial cell activation and the anticryptococcal efficacy induced by anti-CD40/IL-2. Interestingly, while peripheral IFN-γ production and microglial cell activation were observed early after treatment, negligible IFN-γ was detected locally in the brain. These studies indicate that immunotherapy using anti-CD40 and IL-2 can augment host immunity directly in the brain against C. neoformans infection and that IFN-γ is essential for this effect.

UR - http://www.scopus.com/inward/record.url?scp=34247554871&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247554871&partnerID=8YFLogxK

M3 - Article

C2 - 17442959

AN - SCOPUS:34247554871

VL - 178

SP - 5753

EP - 5761

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -