Antibody-mediated protection in murine Cryptococcus neoformans infection is associated with pleotrophic effects on cytokine and leukocyte responses

Marta Feldmesser, Aron Mednick, Arturo Casadevall

Research output: Contribution to journalArticle

Abstract

Cryptococcus neoformans, an encapsulated yeast, is a common cause of life-threatening meningoencephalitis in immunosuppressed patients. We previously observed that administration of a monoclonal antibody (MAb) to the capsular polysaccharide to mice with pulmonary infection prolonged survival and enhanced granulomatous inflammation without reducing lung CFU. To understand the mechanism of MAb action, we studied leukocyte recruitment and cytokine profiles in lungs of A/JCr mice. B lymphocytes were the predominant cell type in lung infiltrates, comprising 15 to 30% of the leukocytes. Despite alterations in histological appearance, fluorescence-activated cell sorter analysis revealed no significant difference in total numbers of lung leukocytes in MAb-treated mice and controls. Differences in the immune response to C. neoformans between MAb-treated mice and controls included (i) an increase in the percentage of granulocytes among lung leukocytes on day 14, (ii) higher macrophage surface expression of CD86 on day 28, (iii) larger amounts of IL-10 in lung homogenates at day 7, (iv) a trend toward smaller amounts of gamma interferon mRNA and protein on day 7, and (v) a smaller increase in the levels of interleukin-4 mRNA and protein on day 7. Hence, the immune responses to C. neoformans infection in the presence and absence of specific antibody were qualitatively similar, and antibody administration was associated with several subtle quantitative differences in immune response parameters that could translate into enhanced survival. MAb may function partly by down-regulating the inflammatory response and reducing host damage. Our findings demonstrate unexpected complexity in the interaction between specific MAb and other components of the host immune response.

Original languageEnglish (US)
Pages (from-to)1571-1580
Number of pages10
JournalInfection and Immunity
Volume70
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Cryptococcus neoformans
Leukocytes
Cytokines
Monoclonal Antibodies
Lung
Antibodies
Infection
Messenger RNA
Meningoencephalitis
Survival
Leukocyte Count
Granulocytes
Interleukin-4
Interleukin-10
Interferon-gamma
Polysaccharides
Proteins
B-Lymphocytes
Yeasts
Fluorescence

ASJC Scopus subject areas

  • Immunology

Cite this

Antibody-mediated protection in murine Cryptococcus neoformans infection is associated with pleotrophic effects on cytokine and leukocyte responses. / Feldmesser, Marta; Mednick, Aron; Casadevall, Arturo.

In: Infection and Immunity, Vol. 70, No. 3, 2002, p. 1571-1580.

Research output: Contribution to journalArticle

@article{9db37504078446cca07e8a02a3e57c06,
title = "Antibody-mediated protection in murine Cryptococcus neoformans infection is associated with pleotrophic effects on cytokine and leukocyte responses",
abstract = "Cryptococcus neoformans, an encapsulated yeast, is a common cause of life-threatening meningoencephalitis in immunosuppressed patients. We previously observed that administration of a monoclonal antibody (MAb) to the capsular polysaccharide to mice with pulmonary infection prolonged survival and enhanced granulomatous inflammation without reducing lung CFU. To understand the mechanism of MAb action, we studied leukocyte recruitment and cytokine profiles in lungs of A/JCr mice. B lymphocytes were the predominant cell type in lung infiltrates, comprising 15 to 30{\%} of the leukocytes. Despite alterations in histological appearance, fluorescence-activated cell sorter analysis revealed no significant difference in total numbers of lung leukocytes in MAb-treated mice and controls. Differences in the immune response to C. neoformans between MAb-treated mice and controls included (i) an increase in the percentage of granulocytes among lung leukocytes on day 14, (ii) higher macrophage surface expression of CD86 on day 28, (iii) larger amounts of IL-10 in lung homogenates at day 7, (iv) a trend toward smaller amounts of gamma interferon mRNA and protein on day 7, and (v) a smaller increase in the levels of interleukin-4 mRNA and protein on day 7. Hence, the immune responses to C. neoformans infection in the presence and absence of specific antibody were qualitatively similar, and antibody administration was associated with several subtle quantitative differences in immune response parameters that could translate into enhanced survival. MAb may function partly by down-regulating the inflammatory response and reducing host damage. Our findings demonstrate unexpected complexity in the interaction between specific MAb and other components of the host immune response.",
author = "Marta Feldmesser and Aron Mednick and Arturo Casadevall",
year = "2002",
doi = "10.1128/IAI.70.3.1571-1580.2002",
language = "English (US)",
volume = "70",
pages = "1571--1580",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - Antibody-mediated protection in murine Cryptococcus neoformans infection is associated with pleotrophic effects on cytokine and leukocyte responses

AU - Feldmesser, Marta

AU - Mednick, Aron

AU - Casadevall, Arturo

PY - 2002

Y1 - 2002

N2 - Cryptococcus neoformans, an encapsulated yeast, is a common cause of life-threatening meningoencephalitis in immunosuppressed patients. We previously observed that administration of a monoclonal antibody (MAb) to the capsular polysaccharide to mice with pulmonary infection prolonged survival and enhanced granulomatous inflammation without reducing lung CFU. To understand the mechanism of MAb action, we studied leukocyte recruitment and cytokine profiles in lungs of A/JCr mice. B lymphocytes were the predominant cell type in lung infiltrates, comprising 15 to 30% of the leukocytes. Despite alterations in histological appearance, fluorescence-activated cell sorter analysis revealed no significant difference in total numbers of lung leukocytes in MAb-treated mice and controls. Differences in the immune response to C. neoformans between MAb-treated mice and controls included (i) an increase in the percentage of granulocytes among lung leukocytes on day 14, (ii) higher macrophage surface expression of CD86 on day 28, (iii) larger amounts of IL-10 in lung homogenates at day 7, (iv) a trend toward smaller amounts of gamma interferon mRNA and protein on day 7, and (v) a smaller increase in the levels of interleukin-4 mRNA and protein on day 7. Hence, the immune responses to C. neoformans infection in the presence and absence of specific antibody were qualitatively similar, and antibody administration was associated with several subtle quantitative differences in immune response parameters that could translate into enhanced survival. MAb may function partly by down-regulating the inflammatory response and reducing host damage. Our findings demonstrate unexpected complexity in the interaction between specific MAb and other components of the host immune response.

AB - Cryptococcus neoformans, an encapsulated yeast, is a common cause of life-threatening meningoencephalitis in immunosuppressed patients. We previously observed that administration of a monoclonal antibody (MAb) to the capsular polysaccharide to mice with pulmonary infection prolonged survival and enhanced granulomatous inflammation without reducing lung CFU. To understand the mechanism of MAb action, we studied leukocyte recruitment and cytokine profiles in lungs of A/JCr mice. B lymphocytes were the predominant cell type in lung infiltrates, comprising 15 to 30% of the leukocytes. Despite alterations in histological appearance, fluorescence-activated cell sorter analysis revealed no significant difference in total numbers of lung leukocytes in MAb-treated mice and controls. Differences in the immune response to C. neoformans between MAb-treated mice and controls included (i) an increase in the percentage of granulocytes among lung leukocytes on day 14, (ii) higher macrophage surface expression of CD86 on day 28, (iii) larger amounts of IL-10 in lung homogenates at day 7, (iv) a trend toward smaller amounts of gamma interferon mRNA and protein on day 7, and (v) a smaller increase in the levels of interleukin-4 mRNA and protein on day 7. Hence, the immune responses to C. neoformans infection in the presence and absence of specific antibody were qualitatively similar, and antibody administration was associated with several subtle quantitative differences in immune response parameters that could translate into enhanced survival. MAb may function partly by down-regulating the inflammatory response and reducing host damage. Our findings demonstrate unexpected complexity in the interaction between specific MAb and other components of the host immune response.

UR - http://www.scopus.com/inward/record.url?scp=0036179288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036179288&partnerID=8YFLogxK

U2 - 10.1128/IAI.70.3.1571-1580.2002

DO - 10.1128/IAI.70.3.1571-1580.2002

M3 - Article

C2 - 11854246

AN - SCOPUS:0036179288

VL - 70

SP - 1571

EP - 1580

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 3

ER -