Diabetes mellitus increases the susceptibility to encephalitozoonosis in mice

Neto, Aldo Francisco Alves; Rocha, P.R.D.; Perez, Elizabeth Christina; Xavier, José Guilherme; Peres, Giovani Bravin; Spadacci-Morena, Diva Denelle; Alvares-Saraiva, Anuska Marcelino; Lallo, Maria Anete

doi:10.1371/journal.pone.0186954

Cited by 11 publications

(7 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cytotoxic effect of this drug is due to the interaction of its alkylating metabolites with DNA. Treatment with Cy reportedly aggravated E. cuniculi infection, rendering it more severe, widespread, and with significantly increased lethality [10, 15, 16, 17]. Contrary to the observations related to the intravenous infection of mice with E. cuniculi [18], in the present study, the fungal load was lower in the immunosuppressed group compared to the mice not treated with cyclophosphamide and then infected with E. cuniculi , which is quite intriguing.…”

Section: Discussioncontrasting

confidence: 76%

Interstitial pneumonia via the oropharyngeal route of infection withEncephalitozoon cuniculiOropharyngeal infection withEncephalitozoon cuniculi

Santos,

da Silva,

de Souza

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Microsporidia causes opportunistic infections in immunosuppressed individuals. Mammals shed these spores of fungi in feces, urine, or respiratory secretions, which could contaminate water and food, thereby reaching the human body and causing infection. The oral route is the most common route of infection, although experiments have demonstrated that intraperitoneal and intravenous routes may also spread infection. Respiratory tract infection, although considered to be possible, has not been reported to date. The present study, therefore, aimed to demonstrate infection with the microsporidia of Encephalitozoon cuniculi via the oropharyngeal route as a model for opportunistic pneumonia. The objectives were the study of opportunistic pneumonia in general while also confirming transmission via the respiratory route to expand the understanding of the epidemiology of zoonoses. C57BL mice, both male and female, up to 12 weeks of age, and free of specific pathogens (SPF) were inoculated (Infected group) or not infected (Non-Infected group) with 1 × 107 spores of E. cuniculi via the oropharyngeal route. The animals immunosuppressed with cyclophosphamide (Cy) were infected (Cy-Infected group) or not infected (Cy-Uninfected group), and then assessed for the influence of immunosuppression on infection. In both groups, animals inoculated with 0.9% saline solution via the oropharyngeal route served as controls (Sham and Cy-Sham groups, respectively). After 14 days of infection, the lungs of all animals were retrieved for histopathological analysis, phenotyping of lung inflammatory cells using flow cytometry, measurement of fungal load using qPCR, and measurement of the serum levels of Th1, Th2, and Th17 cytokines. The results revealed that the infected animals developed interstitial pneumonia characterized by perialveolar inflammatory infiltrative lesions with a predominance of lymphocytes and plasma cells. However, the fungal load and the extent of the inflammatory infiltrate were relatively lower in the Cy-Infected group, with a predominance of the CD8+ T lymphocyte population in the lungs compared to Infected group. In the Infected group not treated with Cy, an increase in the population of alveolar macrophages (F4/80+CD11b-SiglecF+) was noted, along with higher fungal load and inflammatory infiltrate in the lungs, indicating a further pronounced Encephalitozoon pneumonia compared to the immunosuppressed animals. The infected groups presented Th1 cytokine profiles, with the Cy-Infected group exhibiting increased Th17 levels. Collectively, these results demonstrated that oropharyngeal infection promoted pneumonia caused by E. cuniculi in mice treated or not with cyclophosphamide, with greater severity occurring in the non-immunosuppressed mice, thereby establishing this model as a suitable one for interstitial pneumonia via aspiration.

show abstract

Section: Discussioncontrasting

confidence: 76%

Interstitial pneumonia via the oropharyngeal route of infection withEncephalitozoon cuniculiOropharyngeal infection withEncephalitozoon cuniculi

Santos,

da Silva,

de Souza

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…In a previous study, we demonstrated that diabetes mellitus (DM) increased the susceptibility of C57BL/6 mice to encephalitozoonosis and DM mice infected with E . cuniculi showed higher levels of IL-6 than DM- uninfected mice, suggesting that DM may also modulate a pro-inflammatory state of the organism [49]. In the current study, we observed an increase in IL-6- in XID APerC after 1 h and 48 h of cultures infection, associated with an increase in the production of IL-10, a fact that suggests an anti-inflammatory effect of IL-6 corroborating the descriptions referring to its pleiotropic behavior, sometimes as a pro-inflammatory cytokine and sometimes as an anti-inflammatory cytokine.…”

Section: Discussionmentioning

confidence: 99%

B-1 cell-mediated modulation of M1 macrophage profile ameliorates microbicidal functions and disrupt the evasion mechanisms of Encephalitozoon cuniculi

et al. 2019

Self Cite

View full text Add to dashboard Cite

Here, we have investigated the possible effect of B-1 cells on the activity of peritoneal macrophages in E. cuniculi infection. In the presence of B-1 cells, peritoneal macrophages had an M1 profile with showed increased phagocytic capacity and index, associated with the intense microbicidal activity and a higher percentage of apoptotic death. The absence of B-1 cells was associated with a predominance of the M2 macrophages, reduced phagocytic capacity and index and microbicidal activity, increased pro-inflammatory and anti-inflammatory cytokines production, and higher percentual of necrosis death. In addition, in the M2 macrophages, spore of phagocytic E. cuniculi with polar tubular extrusion was observed, which is an important mechanism of evasion of the immune response. The results showed the importance of B-1 cells in the modulation of macrophage function against E. cuniculi infection, increasing microbicidal activity, and reducing the fungal mechanisms involved in the evasion of the immune response.

show abstract

“…However, diabetes is considered a risk factor for opportunistic infections. Experimental infection of diabetic mice with E. cuniculi resulted in more symptoms and a higher pathogen burden than in nondiabetic animals ( 12 ); indeed, the woman with diabetes in our study experienced more severe symptoms, which led to serious impairments in everyday functioning.…”

Section: Discussionmentioning

confidence: 54%

Encephalitozoon cuniculi and Extraintestinal Microsporidiosis in Bird Owners

Kicia¹,

Zajączkowska²,

Kváč³

et al. 2022

Emerg. Infect. Dis.

View full text Add to dashboard Cite

We identified Encephalitozoon cuniculi genotype II parasites as a cause of extraintestinal microsporidiosis in 2 owners of birds also infected with E. cuniculi . Patients experienced long-lasting nonspecific symptoms; the disease course was more progressive in a patient with diabetes. Our findings suggest direct bird-to-human transmission of this pathogen.

show abstract

Diabetes mellitus increases the susceptibility to encephalitozoonosis in mice

Cited by 11 publications

References 48 publications

Interstitial pneumonia via the oropharyngeal route of infection withEncephalitozoon cuniculiOropharyngeal infection withEncephalitozoon cuniculi

Interstitial pneumonia via the oropharyngeal route of infection withEncephalitozoon cuniculiOropharyngeal infection withEncephalitozoon cuniculi

B-1 cell-mediated modulation of M1 macrophage profile ameliorates microbicidal functions and disrupt the evasion mechanisms of Encephalitozoon cuniculi

Encephalitozoon cuniculi and Extraintestinal Microsporidiosis in Bird Owners

Contact Info

Product

Resources

About