Pneumonic Plague in Monkeys: An Electron Microscope Study

Abstract

The Infection of monkey vngaS by Pasteurelia Peipif was studied with the electron microscope. The disease was fizst apparent clinically at 60 to 70 hours and pathologically &t 72 hours. At this time, the initial response seen with the light sicroscope was alveolar edema with massive proliferation of c•anisms. With the electron microscope, interstitial edema around veins and bronchi was the earliest observed response to the presence of numerous intra-alveoler bacilli. Earty in the disease, before the onset of a leukocytic exudate, interstitial fluid also accumulated in the form of subepithelial blebe. No evidence of significant vascular damage was found to accouut for the marked increate in permeability, even with the aid of intravenous injections of colloidal carbon prior to sacrifice. Leukocytic and mast cell factors iu the pathogenesis of the edema appear unlikely. Once the cellular comopnent of the reaction developed, P. a resisted both phagocytosis by polymorphonuclear neutrophils and intracellular digestion by iononuclear phagocytea. Invasion of the tissues by the organism was observed only in the advanced stages of the pneumonia, when all components of the alveolar septa were undergoing necrosis. 1IPneumonic plague is characterized by extensive intra-alveolar edema containing myriads of Pasteurella pestis prior to any significant leukocytic exudate or damage to lung tissueT, when studied by light microscopy.Infected edema fluid is al'so found at the margins of consolidated areas and is the initial change in secondary lesions. 1Other bacterial pneumonias, such as pneumococcal, seem to have a similar pathogenesis, both in the rare human cases with abbreviated disease due to intervening accident? and in experimental animals, 3 but they differ from plague in the more rapid addition of leukocytes, fibrin, and red blood cells to the exudate.The electron microscope has been successfully employed in\ the study of a variety of inflammatory reactions and their components, such as leukocyte migration,' phagocytosis, 5 0 5 and vascular permeability,' but there have been few reports of the ultrastructural manifestations of bacterial pneumonia.•feIn view of the value of electron microscopy in detecting tissue damage in experimental pulmonary edema prior to the appearance of lesions visible with the light microscope,8's it seemed appropriate to examine the lungs of animals exposed to aerosols of P.. pestis in order to describe the ultrastructural changes in necrotizing pneumonia and, hopefully, to determine the pathogenesis of the extensive, early edema. II. MATFTIALS AND EIIODSA. ANIMALS Rhesus monkeys (Macac& mulatta) imported from India were housed locally for at least 90 days before use. Young adults of both sexes weighing between 2.6 and 3.25 kg were housed in paire and were fed Purina monkey chow* a"d water ad libitum. Tuberculin testing was performed monthly, and ot.'-o :negative reactors were used. B. ORGANISH AND EXPOSURESThe KIM-10 strain of P. Pestis was used. The isolation, maintenance, and cultural characte...

Adhesive Properties of YapV and Paralogous Autotransporter Proteins of Yersinia pestis

“…YapV was previously reported to bind to N-WASP (27); however, the biological relevance of this property remains unclear considering the expected separate compartmentalization of YapV and N-WASP. Even though Y. pestis can be detected in macrophages, particularly early during infection (47,48), Y. pestis is not known to reach the host cytosol, where N-WASP is located. In addition, whether the passenger domain of an autotransporter protein can be translocated or injected into the host cytosol remains to be demonstrated.…”

Recent Advancement in the Development of Vaccines Against Y. pestis - A Potential Agent of Bioterrorism

“…However, Y.pestis bacilli were detected in spleen cells and in CD11b-expressing macrophages when mice were infected subcutaneously (Lukaszewski et al, 2005). In addition, studies of pneumonic plague in nonhuman primates have documented the presence of intact Y. pestis within alveolar macrophages (Finegold et al, 1969;Davis et al, 1996). Electron microscopy confirmed the presence of alveolar macrophages containing intact bacilli in the lungs of aerosol-infected macaques (Finegold et al, 1969).…”

Identification of host factors required for Yersinia pestis macrophage intracellular survival and their impact on vacuole maturation, acidification and trafficking.

“…In contrast, when a macrophage or monocyte phagocytizes Y. pestis, the bacterium prevents killing within these cells and is capable of establishing an intracellular niche [51,54,55,57,59,82,83]. In further support of this, Y. pestis infected rodents and nonhuman primates show bacteria association with macrophages, but to a lesser extent neutrophils from within the same infected host [49,53,58,84].…”

“…Y. pestis ΔphoP mutants are defective for intracellular survival and exhibit a higher LD50 with an extended time to death [56,83,90,151]. The role of macrophages during pathogenesis is further emphasized by findings that Y. pestis predominately associates with macrophages and not neutrophils in infected rodents and nonhuman primates [49,53,58,84].…”

“…In vivo, intracellular Y. pestis are recovered from macrophages isolated from both infected nonhuman primates and rodents, but rarely from neutrophils isolated from the same animals [49,58,84]. Ye and colleagues further showed lower bacterial burdens in transgenic MaFIA mice selectively depleted of macrophage/dendritic cell populations, suggesting that macrophages are required to establish acute infection [52].…”