The relative susceptibility of mouse strains to pulmonary Cryptococcus neoformans infection is associated with pleiotropic differences in the immune response

Oscar Zaragoza, Mauricio Alvarez, Andrew Telzak, Johanna Rivera, Arturo Casadevall

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

CBA/J mice were highly susceptible to intratracheal (i.t.) Cryptococcus neoformans infection relative to BALB/c mice, while both strains were equally susceptible to intravenous (i.v.) infection. Increased susceptibility in i.t. infection was associated with higher brain CFU, lower serum immunoglobulin M (IgM) and IgG responses to glucuronoxylomannan (GXM), lack of IgE regulation during infection, and alveolar macrophage permissiveness to intracellular replication in vitro. In contrast, for BALB/c mice, relative resistance was associated with increased interleukin-12 (IL-12) and decreased IL-10 pulmonary levels. In CBA/J mice, relative susceptibility was associated with a decreased proportion of CD4+ and CD8+ T cells and an increase in macrophage percentage in pulmonary infiltrates. In contrast, no significant differences in these cytokines or cell recruitment were observed in the i.v. model, consistent with no differences in the survival rate. Passive antibody (Ab) protection experiments revealed a prozone effect in the BALB/c mice with i.v. infection, such that Ab efficacy decreased at higher doses. In the i.t. model using CBA/J mice, low Ab doses were disease enhancing and protection was observed only at high doses. Our results show (i) that differences in mouse strain susceptibility are a function of the infection model, (ii) that susceptibility to pulmonary infection was associated with macrophage permissiveness for intracellular replication, and (iii) that the efficacy of passive Ab in pulmonary infection is a function of dose and mouse strain. The results highlight significant differences in the pathogenesis of cryptococcal infection among inbred mice and associate their relative susceptibility with differences in numerous components of the innate and adaptive immune responses.

Original languageEnglish (US)
Pages (from-to)2729-2739
Number of pages11
JournalInfection and Immunity
Volume75
Issue number6
DOIs
StatePublished - Jun 2007

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Cryptococcus neoformans
Lung
Infection
Inbred CBA Mouse
Permissiveness
Antibodies
Macrophages
Alveolar Macrophages
Adaptive Immunity
Interleukin-12
Innate Immunity
Interleukin-10
Immunoglobulin E
Immunoglobulin M
Immunoglobulin G
Cytokines
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

The relative susceptibility of mouse strains to pulmonary Cryptococcus neoformans infection is associated with pleiotropic differences in the immune response. / Zaragoza, Oscar; Alvarez, Mauricio; Telzak, Andrew; Rivera, Johanna; Casadevall, Arturo.

In: Infection and Immunity, Vol. 75, No. 6, 06.2007, p. 2729-2739.

Research output: Contribution to journalArticle

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