Human IgM inhibits the formation of titan-like cells in cryptococcus neoformans

Trevijano-Contador Nuria Trevijano-Contador, Kaila M. Pianalto, Connie B. Nichols, Oscar Zaragoza, J. Andrew Alspaugh, Liise Anne Pirofski

Research output: Contribution to journalArticle

Abstract

Human studies have shown associations between cryptococcal meningitis and reduced IgM memory B cell levels, and studies in IgM- and/or B cell-deficient mice have demonstrated increased Cryptococcus neoformans dissemination from lungs to brain. Since immunoglobulins are part of the immune milieu that C. neoformans confronts in a human host, and its ability to form titan cells is an important virulence mechanism, we determined the effect of human immunoglobulins on C. neoformans titan cell formation in vitro. (i) Fluorescence microscopy showed normal human IgG and IgM bind C. neoformans. (ii) C. neoformans grown in titan cellinducing medium with IgM, not IgG, inhibited titan-like cell formation. (iii) Absorption of IgM with laminarin or curdlan (branched and linear 1-3-beta-D-glucans, respectively) decreased this effect. (iv) Transmission electron microscopy revealed that cells grown with IgM had small capsules and unique features not seen with cells grown with IgG. (v) Comparative transcriptional analysis of cell wall, capsule, and stress response genes showed that C. neoformans grown with IgM, not IgG or phosphate-buffered saline (PBS), had decreased expression of chitin synthetase, CHS1, CHS2, and CHS8, and genes encoding cell wall carbohydrate synthetases α-1- 3-glucan (AGS1) and β-1,3-glucan (FKS1). IgM also decreased expression of RIM101 and HOG1, genes encoding central regulators of C. neoformans stress response pathways and cell morphogenesis. Our data show human IgM affects C. neoformans morphology in vitro and suggest that the hypothesis that human immunoglobulins may affect C. neoformans virulence in vivo warrants further investigation.

Original languageEnglish (US)
Article numbere00046-20
JournalInfection and immunity
Volume88
Issue number4
DOIs
StatePublished - Mar 1 2020

Keywords

  • Beta glucans
  • Capsule
  • Cell wall
  • Cryptococcosis
  • Cryptococcus neoformans
  • IgG
  • IgM
  • IgM memory B cells
  • Natural antibodies
  • Titan cells

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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  • Cite this

    Nuria Trevijano-Contador, T-C., Pianalto, K. M., Nichols, C. B., Zaragoza, O., Alspaugh, J. A., & Pirofski, L. A. (2020). Human IgM inhibits the formation of titan-like cells in cryptococcus neoformans. Infection and immunity, 88(4), [e00046-20]. https://doi.org/10.1128/IAI.00046-20