Early interaction of Yersinia pestis with APCs in the lung.
Despite the importance of pneumonic plague, little is known of the early pulmonary immune responses that occur following inhalation of Yersinia pestis. Therefore, we conducted studies to identify the early target cells for uptake of Y. pestis in the lungs following intratracheal or i.v. inoculation. Following intratracheal inoculation, Y. pestis was rapidly internalized primarily by a distinctive population of CD11c+DEC-205+CD11b- cells in the airways, whereas i.v. inoculation resulted in uptake primarily by CD11b+CD11c- macrophages and granulocytes in lung tissues. The airway cells internalized and were infected by Y. pestis, but did not support active replication of the organism. Intratracheal inoculation of Y. pestis resulted in rapid activation of airway CD11c+ cells, followed within 24 h by the selective disappearance of these cells from the airways and lungs and the accumulation of apoptotic CD11c+ cells in draining lymph nodes. When CD11c+ cells in the airways were depleted using liposomal clodronate before infection, this resulted in a significantly increased replication of Y. pestis in the lungs and dissemination to the spleen and draining lymph nodes. These findings suggest that CD11c+ cells in the airways play an important role in suppressing the initial replication and dissemination of inhaled Y. pestis, although these results will also require confirmation using fully virulent strains of Y. pestis. Depletion of these airway cells by Y. pestis may therefore be one strategy the organism uses to overcome pulmonary defenses following inhalation of the organism.
Bosio
Catharine M
CM
Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences,Colorado State University, Fort Collins, 80523, USA.
Goodyear
Andrew W
AW
Dow
Steven W
SW
D000280:Administration, Inhalation; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D039521:CD11c Antigen / Q000378:metabolism; D002465:Cell Movement; D005260:Female; D007275:Injections, Intravenous; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010930:Plague / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D015010:Yersinia pestis / Q000276:immunology* / Q000472:pathogenicity
D039521:CD11c Antigen; C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D019707:Receptors, Chemokine