title: 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.
authors: Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors: Felicia D
authors: FD
authors: Langel
authors: Molecular and Translational Sciences Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
authors: Chih-Yuan
authors: CY
authors: Chiang
authors: SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors: Douglas
authors: D
authors: Lane
authors: SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors: Tara
authors: T
authors: Kenny
authors: Molecular and Translational Sciences Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
authors: Jenifer F
authors: JF
authors: Ojeda
authors: Genomics Institute of the Novartis Research Foundation, San Diego, California, United States of America.
authors: Yang
authors: Y
authors: Zhong
authors: Genomics Institute of the Novartis Research Foundation, San Diego, California, United States of America.
authors: Jianwei
authors: J
authors: Che
authors: Genomics Institute of the Novartis Research Foundation, San Diego, California, United States of America.
authors: Yingyao
authors: Y
authors: Zhou
authors: Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
authors: Wilson
authors: W
authors: Ribot
authors: Perkin Elmer, Waltham, Massachusetts, United States of America.
authors: Krishna P
authors: KP
authors: Kota
authors: Molecular and Translational Sciences Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
authors: Sina
authors: S
authors: Bavari
authors: Molecular and Translational Sciences Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
authors: Rekha G
authors: RG
authors: Panchal
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001408:Bacillus anthracis; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D008253:Macaca mulatta; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D010587:Phagocytosis / Q000276:immunology; D013171:Spores, Bacterial / Q000276:immunology / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial