Resident CD11c+ lung cells are impaired by anthrax toxins after spore infection.
Bacillus anthracis secretes 2 toxins: lethal toxin (LT) and edema toxin (ET). We investigated their role in the physiopathologic mechanisms of inhalational anthrax by evaluating murine lung dendritic cell (LDC) functions after infection with B. anthracis strains secreting LT, ET, or both or with a nontoxinogenic strain. Three lung cell populations gated on CD11c/CD11b expression were obtained after lung digestion: (1) CD11c(high)/CD11b(low) (alveolar macrophages), (2) CD11c(intermediate (int))/CD11b(int) (LDCs), and (3) CD11c(low)/CD11b(high) (interstitial macrophages or monocytes). After infection with LT-secreting strains, a decrease in costimulatory molecule expression on LDCs was observed. All CD11c+ cells infected with a nontoxinogenic strain secreted tumor necrosis factor (TNF)- alpha , interleukin (IL)-10, and IL-6. LT-secreting strains inhibited overall cytokine secretion, whereas the ET-secreting strain inhibited only TNF- alpha secretion and increased IL-6 secretion. Similar results were obtained after preincubation with purified toxins. Our results suggest that anthrax toxins secreted during infection impair LDC function and suppress the innate immune response.
Cleret
Aurelie
A
Unité d'Immunobiologie, Département de Biologie des Agents Transmissibles, Centre de Recherche du Service de Santé des Armées, La Tronche, France.
Quesnel-Hellmann
Anne
A
Mathieu
Jacques
J
Vidal
Dominique
D
Tournier
Jean-Nicolas
JN
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology* / Q000633:toxicity*; D001408:Bacillus anthracis / Q000276:immunology / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000276:immunology* / Q000633:toxicity*; D039521:CD11c Antigen / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000382:microbiology; D015870:Gene Expression / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects; D010587:Phagocytosis / Q000276:immunology; D013171:Spores, Bacterial / Q000276:immunology / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D039521:CD11c Antigen; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C030325:anthrax toxin; D016753:Interleukin-10