Skip to main content

Cryptococcus neoformans Rim101 is associated with cell wall remodeling and evasion of the host immune responses.

Publication ,  Journal Article
O'Meara, TR; Holmer, SM; Selvig, K; Dietrich, F; Alspaugh, JA
Published in: mBio
January 15, 2013

UNLABELLED: Infectious microorganisms often play a role in modulating the immune responses of their infected hosts. We demonstrate that Cryptococcus neoformans signals through the Rim101 transcription factor to regulate cell wall composition and the host-pathogen interface. In the absence of Rim101, C. neoformans exhibits an altered cell surface in response to host signals, generating an excessive and ineffective immune response that results in accelerated host death. This host immune response to the rim101Δ mutant strain is characterized by increased neutrophil influx into the infected lungs and an altered pattern of host cytokine expression compared to the response to wild-type cryptococcal infection. To identify genes associated with the observed phenotypes, we performed whole-genome RNA sequencing experiments under capsule-inducing conditions. We defined the downstream regulon of the Rim101 transcription factor and determined potential cell wall processes involved in the capsule attachment defects and altered mechanisms of virulence in the rim101Δ mutant. The cell wall generates structural stability for the cell and allows the attachment of surface molecules such as capsule polysaccharides. In turn, the capsule provides an effective mask for the immunogenic cell wall, shielding it from recognition by the host immune system. IMPORTANCE: Cryptococcus neoformans is an opportunistic human pathogen that is a significant cause of death in immunocompromised individuals. There are two major causes of death due to this pathogen: meningitis due to uncontrolled fungal proliferation in the brain in the face of a weakened immune system and immune reconstitution inflammatory syndrome characterized by an overactive immune response to subclinical levels of the pathogen. In this study, we examined how C. neoformans uses the conserved Rim101 transcription factor to specifically remodel the host-pathogen interface, thus regulating the host immune response. These studies explored the complex ways in which successful microbial pathogens induce phenotypes that ensure their own survival while simultaneously controlling the nature and degree of the associated host response.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

mBio

DOI

EISSN

2150-7511

Publication Date

January 15, 2013

Volume

4

Issue

1

Location

United States

Related Subject Headings

  • Transcription Factors
  • Regulon
  • Mice, Inbred C57BL
  • Mice
  • Lung
  • Immune Evasion
  • Host-Pathogen Interactions
  • Gene Expression Regulation, Fungal
  • Gene Expression Profiling
  • Gene Deletion
 

Citation

APA
Chicago
ICMJE
MLA
NLM
O’Meara, T. R., Holmer, S. M., Selvig, K., Dietrich, F., & Alspaugh, J. A. (2013). Cryptococcus neoformans Rim101 is associated with cell wall remodeling and evasion of the host immune responses. MBio, 4(1). https://doi.org/10.1128/mBio.00522-12
O’Meara, Teresa R., Stephanie M. Holmer, Kyla Selvig, Fred Dietrich, and J Andrew Alspaugh. “Cryptococcus neoformans Rim101 is associated with cell wall remodeling and evasion of the host immune responses.MBio 4, no. 1 (January 15, 2013). https://doi.org/10.1128/mBio.00522-12.
O’Meara TR, Holmer SM, Selvig K, Dietrich F, Alspaugh JA. Cryptococcus neoformans Rim101 is associated with cell wall remodeling and evasion of the host immune responses. mBio. 2013 Jan 15;4(1).
O’Meara, Teresa R., et al. “Cryptococcus neoformans Rim101 is associated with cell wall remodeling and evasion of the host immune responses.MBio, vol. 4, no. 1, Jan. 2013. Pubmed, doi:10.1128/mBio.00522-12.
O’Meara TR, Holmer SM, Selvig K, Dietrich F, Alspaugh JA. Cryptococcus neoformans Rim101 is associated with cell wall remodeling and evasion of the host immune responses. mBio. 2013 Jan 15;4(1).

Published In

mBio

DOI

EISSN

2150-7511

Publication Date

January 15, 2013

Volume

4

Issue

1

Location

United States

Related Subject Headings

  • Transcription Factors
  • Regulon
  • Mice, Inbred C57BL
  • Mice
  • Lung
  • Immune Evasion
  • Host-Pathogen Interactions
  • Gene Expression Regulation, Fungal
  • Gene Expression Profiling
  • Gene Deletion