New Insight into Immunity and Immunopathology of Rickettsial Diseases

Mansueto, Pasquale; Vitale, Giustina; Cascio, Antonio; Seidita, Aurelio; Pepe, Ilenia; Carroccio, Antonio; Rosa, Salvatore Di; Rini, Giovam Battista; Cillari, Enrìco; Walker, David H.

doi:10.1155/2012/967852

Cited by 116 publications

(102 citation statements)

References 122 publications

(133 reference statements)

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“…They are divided in 4 groups based on their genotypic characteristics: Spotted fever group (R. rickettsii, R. conorii, R. parkeri, and several others), typhus group (R. prowazekii and R. typhi), transitional group (R. felis, R. akari, and R. australis), and the nonpathogenic ancestral group (R. bellii and R. canadensis) (Mansueto et al 2012). R. typhi (known in the old literature as R. mooseri) and R. felis are the etiological agents of murine typhus and flea-borne spotted fever, respectively.…”

Section: R Ickettsioses Are Vector-borne Zoonotic Infectionsmentioning

confidence: 99%

Flea-Borne Rickettsioses in the North of Caldas Province, Colombia

Hidalgo

Montoya

Martínez

et al. 2013

Vector-Borne and Zoonotic Diseases

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Rickettsia typhi and R. felis are the etiological agents of murine typhus and flea-borne spotted fever, respectively. Both are emerging acute febrile zoonotic diseases for which fleas are vectors; they also have similar clinical characteristics and global distribution. In 2005, we identified the circulation of murine typhus in 6 towns within the mountainous coffee-growing area north of Caldas, Colombia. We now report the specific seroprevalence against R. typhi and R. felis, and associated risk factors in 7 towns of this province. The combined seroprevalence against the 2 flea-borne rickettsioses is the highest yet reported in the literature: 71.7% (17.8% for R. felis, 25.2% for R. typhi, and 28.7% for both). We also report a prospective analysis of 26 patients with a febrile illness compatible with rickettsioses, including murine typhus; 9 of these patients had a rickettsiosis. This supports our sero-epidemiological results and highlights the diagnostic complexity of febrile syndromes in this region.

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Section: R Ickettsioses Are Vector-borne Zoonotic Infectionsmentioning

confidence: 99%

Flea-Borne Rickettsioses in the North of Caldas Province, Colombia

Hidalgo

Montoya

Martínez

et al. 2013

Vector-Borne and Zoonotic Diseases

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“…Based on phylogenetic analyses, the family Rickettsiaceae is subdivided into three major groups, the spotted fever group (SFG), the typhus group (TG), and the scrub typhus group (1,2). The majority of rickettsiae identified so far are SFG bacteria.…”

mentioning

confidence: 99%

Persisting Rickettsia typhi Causes Fatal Central Nervous System Inflammation

et al. 2016

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bRickettsioses are emerging febrile diseases caused by obligate intracellular bacteria belonging to the family Rickettsiaceae. Rickettsia typhi belongs to the typhus group (TG) of this family and is the causative agent of endemic typhus, a disease that can be fatal. In the present study, we analyzed the course of R. typhi infection in C57BL/6 RAG1 ؊/؊ mice. Although these mice lack adaptive immunity, they developed only mild and temporary symptoms of disease and survived R. typhi infection for a long period of time. To our surprise, 3 to 4 months after infection, C57BL/6 RAG1 ؊/؊ mice suddenly developed lethal neurological disorders. Analysis of these mice at the time of death revealed high bacterial loads, predominantly in the brain. This was accompanied by a massive expansion of microglia and by neuronal cell death. Furthermore, high numbers of infiltrating CD11b ؉ macrophages were detectable in the brain. In contrast to the microglia, these cells harbored R. typhi and showed an inflammatory phenotype, as indicated by inducible nitric oxide synthase (iNOS) expression, which was not observed in the periphery. Having shown that R. typhi persists in immunocompromised mice, we finally asked whether the bacteria are also able to persist in resistant C57BL/6 and BALB/c wild-type mice. Indeed, R. typhi could be recultivated from lung, spleen, and brain tissues from both strains even up to 1 year after infection. This is the first report demonstrating persistence and reappearance of R. typhi, mainly restricted to the central nervous system in immunocompromised mice.

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“…Rickettsiae are obligate intracellular parasites with prominent tropism for the host vascular endothelial cells [3,4]. The rickettsial diseases are still not quite thoroughly studied as to some aspects of their pathogenesis and especially to issues that concern the crucial signals for apoptosis in the targeted microvascular endothelial cells [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…The programmed cell death in MSF is among the www.fhc.viamedica.pl phenomena that are still inadequately elucidated [4][5][6]9]. We were prompted to conduct the present study by the scantiness of studies on apoptosis in the microvascular endothelial cells in rickettsial diseases and by practically nonexistent research on patients with MSF [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Changes of Bcl-2, Bax and Caspase-3 expression in the dermal microvascular endothelial cells and the epidermal layers of the eschar (tache noire) in patients with Mediterranean spotted fever

Baltadzhiev

Delchev

2013

Folia Histochem Cytobiol.

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Abstract:Mediterranean spotted fever (MSF) is widely prevalent in many endemic regions in Bulgaria. The disease is still not quite thoroughly studied as to some aspects of its pathogenesis and especially to issues that concern the crucial signals for apoptosis in the target microvascular endothelial cells. To study the expression of Bcl-2 family proteins and Caspase-3 in the dermal capillary endothelial cells from skin papules and in the eschar (tache noire) epidermal layers of patients with MSF so that we can establish apoptotic processes and the time of their occurrence and deployment. Immunohistochemical reactions for Bcl-2, Bax and Caspase-3 were obtained in slices of punch-biopsies taken from papules of the skin rash and from the eschars of eight patients with MSF. The average intensity of the reactions was compared with that in control punch-biopsy slices from four healthy subjects. MSF was etiologically confirmed in all patients by positive antibody response to a specific antigen, Rickettsia conorii, with indirect immunofluorescent assay performed by the Rickettsial Reference Laboratory. The immune reaction for Bcl-2 was found to be poorly expressed in the capillary endothelial cells of skin papules of patients without any differences from controls. The expression of Bax and Caspase-3 was strongly upregulated in comparison with the controls. The Bcl-2/Bax ratio was significantly decreased. Microvascular endothelial cells of the eschar showed similar changes. While the Bcl-2/Bax ratio decreased in the epidermal layers of the eschar "tache noire", there were no changes in the intensity of the immunoreactivity of Caspase-3 as compared with controls. The upregulation of Bax and Caspase-3 is an indication of ongoing apoptotic processes in the dermal microvascular endothelial cells of MSF patients. The epidermal layers of the eschar showed increased sensitivity to apoptosis, however, executive phase of apoptosis did not occur.

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New Insight into Immunity and Immunopathology of Rickettsial Diseases

Cited by 116 publications

References 122 publications

Flea-Borne Rickettsioses in the North of Caldas Province, Colombia

Flea-Borne Rickettsioses in the North of Caldas Province, Colombia

Persisting Rickettsia typhi Causes Fatal Central Nervous System Inflammation

Changes of Bcl-2, Bax and Caspase-3 expression in the dermal microvascular endothelial cells and the epidermal layers of the eschar (tache noire) in patients with Mediterranean spotted fever

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