A New Target Organ of Leishmania (Viannia) braziliensis Chronic Infection: The Intestine

Gessilda de Alcantara Nogueira-Melo,Thaís Gomes Verzignassi Silveira,Lainy Leiny de Lima,Andrea Claudia Bekner Silva Fernandes,Amanda Gubert Alves dos Santos,Maria Gabriela Lima da Silva,Erick Lincoln Carneiro,Debora de Mello Gonçales Sant’Ana

doi:10.3389/fcimb.2021.687499

Gessilda de Alcantara Nogueira-Melo, Thaís Gomes Verzignassi Silveira + Show 6 more

Open Access

https://doi.org/10.3389/fcimb.2021.687499

Copy DOI

Abstract

Leishmania (Viannia) braziliensis is one of the main causes of cutaneous leishmaniasis in the Americas. This species presents genetic polymorphism that can cause destructive lesions in oral, nasal, and oropharyngeal tracts. In a previous study, the parasite caused several histopathological changes to hamster ileums. Our study evaluates immune response components, morphological changes, and effects on neurons in the ileums of hamsters infected by three different strains of L. (V.) braziliensis in two infection periods. For the experiment, we separated hamsters into four groups: a control group and three infected groups. Infected hamsters were euthanized 90- or 120-days post infection. We used three strains of L. (V.) braziliensis: the reference MHOM/BR/1975/M2903 and two strains isolated from patients who had different responses to Glucantime® treatment (MHOM/BR/2003/2314 and MHOM/BR/2000/1655). After laparotomy, ileums were collected for histological processing, biochemical analysis, and evaluation of neurons in the myenteric and submucosal plexuses of the enteric nervous system (ENS). The results demonstrated the increase of blood leukocytes after the infection. Optical microscopy analysis showed histopathological changes with inflammatory infiltrates, edemas, ganglionitis, and Leishmania amastigotes in the ileums of infected hamsters. We observed changes in the organ histoarchitecture of infected hamsters when compared to control groups, such as thicker muscular and submucosa layers, deeper and wider crypts, and taller and broader villi. The number of intraepithelial lymphocytes and TGF-β-immunoreactive cells increased in all infected groups when compared to the control groups. Mast cells increased with longer infection periods. The infection also caused remodeling of intestinal collagen and morphometry of myenteric and submucosal plexus neurons; but this effect was dependent on infection duration. Our results show that L. (V.) braziliensis infection caused time-dependent alterations in hamster ileums. This was demonstrated by the reduction of inflammatory cells and the increase of tissue regeneration factors at 120 days of infection. The infected groups demonstrated different profiles in organ histoarchitecture, migration of immune cells, and morphometry of ENS neurons. These findings suggest that the small intestine (or at least the ileum) is a target organ for L. (V.) braziliensis infection, as the infection caused changes that were dependent on duration and strain.

Highlights

Leishmania (Viannia) braziliensis is one of the main species that causes cutaneous and mucocutaneous leishmaniasis in the Americas (Patino et al, 2020)
Consistency of feces, and appearance of hair did not change during the experimental period when compared the groups
Due to the clinical/epidemiological importance (Ministério da Saúde, 2017; Conceição-Silva and Morgado, 2019; World Health Organization, 2020) of the disease and its ability to use genetic diversity to create more aggressive forms (Guimarães et al, 2016; Rugani et al, 2018), our study evaluated the changes in hamster ileums at 90 days and 120 days of infection from one reference parasite strain and two clinically-isolated strains

Summary

Introduction

Leishmania (Viannia) braziliensis is one of the main species that causes cutaneous and mucocutaneous leishmaniasis in the Americas (Patino et al, 2020). (V.) braziliensis and disease severity are related to the immune system (Fernandes et al, 2016), genetic factors, the clinical condition of the host (Quaresma et al, 2018), and the inoculum (Ribeiro-Romão et al, 2014) and strain of the parasite (Vieira et al, 2019); this species presents high levels of genetic polymorphism (Patino et al, 2020). Different strains found in the same region can cause different clinical forms (Guimarães et al, 2016; Quaresma et al, 2018; Rugani et al, 2018) and therapeutic responses (Fernandes et al, 2016; Gagini et al, 2017), even in the same patient (Hoyos et al, 2019). The DNA of the parasite has been detected in bone marrow of immunocompromised patients (Gontijo et al, 2002; Silva et al, 2002)

Objectives

Methods

Results

Conclusion