Galactoxylomannan-mediated immunological paralysis results from specific B cell depletion in the context of widespread immune system damage

Magdia De Jesus, André Moraes Nicola, Susana Frases, Ian R. Lee, Steven Mieses, Arturo Casadevall

Research output: Contribution to journalArticle

Abstract

The mechanisms responsible for polysaccharide-induced immunological paralysis have remained unexplained almost a century after this phenomenon was first described. Cryptococcus neoformans capsular polysaccharides glucuronoxylomannan and galactoxylomannan (GalXM) elicit little or no Ab responses. This study investigates the immunological and biological effects of GalXM in mice. GalXM immunization elicits a state of immunological paralysis in mice characterized by the disappearance of Ab-producing cells in the spleen. Immunological paralysis and lack of immunogenicity could not be overcome by immunization with GalXM conjugated to a protein carrier, Bacillus anthracis protective Ag. Additionally, immunization with GalXM in either complete or IFA was associated with spleen enlargement in BALB/c mice. TUNEL and flow cytometry revealed widespread apoptosis in the spleen after GalXM administration. Administration of a cocktail of caspase-3 inhibitor Z-DEVD-FMK and general caspase inhibitor Z-VAD-FMK or Fas-deficient mice abrogated the complete disappearance of Ab-producing cells. Analysis of spleen cytokine expression in response to GalXM systemic injection revealed that GalXM down-regulated the production of inflammatory cytokines. Hence, we conclude that GalXM-induced immune paralysis is a result of specific B cell depletion mediated by its proapoptotic properties in the context of widespread dysregulation of immune function.

Original languageEnglish (US)
Pages (from-to)3885-3894
Number of pages10
JournalJournal of Immunology
Volume183
Issue number6
DOIs
StatePublished - Sep 15 2009
Externally publishedYes

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Paralysis
Immune System
B-Lymphocytes
Spleen
Immunization
Caspase Inhibitors
Polysaccharides
Cytokines
galactoxylomannan
Bacillus anthracis
Cryptococcus neoformans
In Situ Nick-End Labeling
Caspase 3
Carrier Proteins
Flow Cytometry
Apoptosis
Injections

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Galactoxylomannan-mediated immunological paralysis results from specific B cell depletion in the context of widespread immune system damage. / De Jesus, Magdia; Nicola, André Moraes; Frases, Susana; Lee, Ian R.; Mieses, Steven; Casadevall, Arturo.

In: Journal of Immunology, Vol. 183, No. 6, 15.09.2009, p. 3885-3894.

Research output: Contribution to journalArticle

De Jesus, Magdia ; Nicola, André Moraes ; Frases, Susana ; Lee, Ian R. ; Mieses, Steven ; Casadevall, Arturo. / Galactoxylomannan-mediated immunological paralysis results from specific B cell depletion in the context of widespread immune system damage. In: Journal of Immunology. 2009 ; Vol. 183, No. 6. pp. 3885-3894.
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