Alveolar macrophages infected with Ames or Sterne strain of Bacillus anthracis elicit differential molecular

Felicia D Langel1, Chih-Yuan Chiang2, Douglas Lane3

  • 1Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.

Plos One
|February 12, 2014
PubMed

Insights

Alveolar macrophages (AMs) respond differently to virulent Bacillus anthracis (Ames) and vaccine (Sterne) strains. Host immune responses, including gene expression, reveal distinct pathways modulated by each B. anthracis strain, impacting pathogenicity.

Area of Science:

  • Immunology
  • Microbiology
  • Genomics

Background:

  • Alveolar macrophages (AMs) are crucial in the innate immune response to inhaled Bacillus anthracis (B. anthracis).
  • The virulent Ames strain possesses an antiphagocytic capsule and lethal toxin, while the attenuated Sterne strain lacks the capsule, serving as a vaccine.
  • Understanding host responses to different B. anthracis strains is vital for comprehending disease pathogenesis.

Purpose of the Study:

  • To investigate cellular-level host responses in rhesus macaque AMs infected with virulent (Ames) and attenuated (Sterne) B. anthracis strains.
  • To identify differentially expressed genes and understand how these host responses contribute to varying pathogenicity.
  • To explore potential common molecular signatures in response to B. anthracis and other pathogens.

Main Methods:

  • Primary rhesus macaque AMs were infected with Ames or Sterne strain spores.
  • Microarray analysis was performed to assess gene expression profiles.
  • Meta-analyses were conducted to compare gene expression with responses to other pathogens.
  • Protein expression data for specific cytokines and chemokines were analyzed.

Main Results:

  • 528 human orthologs were differentially expressed in AMs infected with either B. anthracis strain.
  • Genes induced by B. anthracis infection showed overlap with those induced by Francisella Novicida and Staphylococcus aureus, suggesting a common immune response signature.
  • Microarray and protein data indicated differential modulation of innate immune sensing, anti-apoptosis, and apoptosis pathways by the two B. anthracis strains.

Conclusions:

  • The observed differences in gene and protein expression between Ames and Sterne strain infections provide insights into the distinct host responses.
  • These differential host responses likely account for the significant difference in pathogenicity between the virulent and vaccine strains of B. anthracis.
  • A common molecular signature may exist for host responses to various bacterial pathogens.