Alveolar Macrophages Infected with Ames or Sterne Strain of Bacillus anthracis Elicit Differential Molecular Expression Patterns

Abstract

Alveolar macrophages (AMs) phagocytose Bacillus anthracis following inhalation and induce the production of pro-inflammatory cytokines and chemokines to mediate the activation of innate immunity. Ames, the virulent strain of B. anthracis, contains two plasmids that encode the antiphagocytic poly-γ-d-glutamic acid capsule and the lethal toxin. The attenuated Sterne strain of B. anthracis, which lacks the plasmid encoding capsule, is widely adapted as a vaccine strain. Although differences in the outcome of infection with the two strains may have originated from the presence or absence of an anti-phagocytic capsule, the disease pathogenesis following infection will be manifested via the host responses, which is not well understood. To gain understanding of the host responses at cellular level, a microarray analysis was performed using primary rhesus macaque AMs infected with either Ames or Sterne spores. Notably, 528 human orthologs were identified to be differentially expressed in AMs infected with either strain of the B. anthracis. Meta-analyses revealed genes differentially expressed in response to B. anthracis infection were also induced upon infections with multiple pathogens such as Francisella Novicida or Staphylococcus aureus. This suggests the existence of a common molecular signature in response to pathogen infections. Importantly, the microarray and protein expression data for certain cytokines, chemokines and host factors provide further insights on how cellular processes such as innate immune sensing pathways, anti-apoptosis versus apoptosis may be differentially modulated in response to the virulent or vaccine strain of B. anthracis. The reported differences may account for the marked difference in pathogenicity between these two strains.

Passive protection against anthrax in mice with plasma derived from horses hyper-immunized againstBacillus anthracisSterne strain

“…The B. anthracis Sterne strain vaccine has been shown to induce a broad humoral response against all three toxin components as well as inducing innate responses and modulating macrophage activity ( Chakrabarty et al, 2006 ; Ivins et al, 1986 ; Langel et al, 2014 ; Little & Knudson, 1986 ). This diverse immune response has been shown to be fully protective in both toxin challenges and fully virulent anthrax infections ( Ivins et al, 1986 ; Jackson, Wright & Armstrong, 1957 ; Little & Knudson, 1986 ; Romanov, 1980 ; Welkos & Friedlander, 1988 ).…”

Effect of over expressing protective antigen on global gene transcription in Bacillus anthracis BH500

“…At the present time, there is no information on gene expression patterns in B. anthracis expressing recombinant proteins at high cell density. Most transcriptome studies in B. anthracis have focused on networks involved in host-pathogen interactions 20 , 21 and metabolism 22 .…”