Distinct courses of infection withLeishmania(L.)amazonensisare observed in BALB/c, BALB/c nude and C57BL/6 mice

Abstract

Leishmania (L.) amazonensis [L. (L.) amazonensis] is widely distributed in Brazil and its symptomatic infections usually lead to few localized lesions and sometimes to diffuse cutaneous form, with nodules throughout the body, anergy to parasite antigens and poor therapeutic response. The variability of these manifestations draws attention to the need for studies on the pathophysiology of infection by this species. In this study, we analysed the course and immunological aspects of L. (L.) amazonensis infection in BALB/c and C57BL/6 strains, both susceptible, but displaying different clinical courses, and athymic BALB/c nude, to illustrate the role of T cell dependent responses. We analysed footpad thickness and parasite burden by in vivo imaging. Furthermore, we evaluated the cellular profile and cytokine production in lymph nodes and the inflammatory infiltrates of lesions. Nude mice showed delayed lesion development and less inflammatory cells in lesions, but higher parasite burden than BALB/c and C57BL/6. BALB/c and C57BL/6 mice had similar parasite burdens, lesion sizes and infiltrates until 6 weeks after infection, and after that C57BL/6 mice controlled the infection. Small differences in parasite numbers were observed in C57BL/6 macrophages in vitro, indicating that in vivo milieu accounts for most differences in infection. We believe our results shed light on the role of host immune system in the course of L. (L.) amazonensis infection by comparing three mouse strains that differ in parasitaemia and inflammatory cells.

Quantitative proteomic analysis of amastigotes from Leishmania (L.) amazonensis LV79 and PH8 strains reveals molecular traits associated with the virulence phenotype

“…amazonensis develop small lesions in C57BL/6 mice. In fact, LV79 lesions in this mouse strain increase until six weeks after inoculation and decrease thereafter, although parasites can still be found in lesions until thirteen weeks post infection [ 30 ]. On the other hand, PH8 strain was shown to generate lesions of increasing size in the same mouse strain [ 31 ].…”

Modulation of Cytokines and Extracellular Matrix Proteins Expression by Leishmania amazonensis in Susceptible and Resistant Mice

“…Depending on the infecting Leishmania species and host genetics, lesions progress into erythematous nodules, indurated plaques, scaly plaques, or ulcers ( Nylén and Eidsmo, 2012 ). The relationship between parasite growth, lesion formation, and immunity has been studied by several authors in different mouse strains ( Lira et al, 2000 ; Cardoso et al, 2010 ; Velasquez et al, 2016 ; Souza et al, 2018 ). Velasquez et al (2016) have shown that L. amazonensis -infected C57BL/6 mice developed smaller lesions that progressed to complete healing, while BALB/c and BALB/c nude mice developed progressive lesions, which correlated to the parasite load.…”

“…The relationship between parasite growth, lesion formation, and immunity has been studied by several authors in different mouse strains ( Lira et al, 2000 ; Cardoso et al, 2010 ; Velasquez et al, 2016 ; Souza et al, 2018 ). Velasquez et al (2016) have shown that L. amazonensis -infected C57BL/6 mice developed smaller lesions that progressed to complete healing, while BALB/c and BALB/c nude mice developed progressive lesions, which correlated to the parasite load. In the present study, a positive correlation between parasite load and lesion size was also found in C57BL/10 mice but not in C3H/He.…”

“…Reduced cellular immunity, with dysfunction of macrophages and/or T cells is responsible for disease progress ( Kong et al, 2017 ). Development of different clinical manifestations, as well as disease severity, has been attributed, not only to the parasite species, but also to the host genetics and immune responses ( Afonso and Scott, 1993 ; Von Stebut and Udey, 2004 ; Rosas et al, 2005 ; Alexander and Brombacher, 2012 ; Velasquez et al, 2016 ; Muxel et al, 2018 ). In comparison to Leishmania major , parasites belonging to the Leishmania mexicana complex show profound differences in the virulence factors, which affect the immune mechanisms that mediate the susceptibility/resistance to infection ( McMahon-Pratt and Alexander, 2004 ).…”

Lymphocytes influence Leishmania major pathogenesis in a strain-dependent manner

“…Some studies showed that lesion development was independent of T/B cells in CL models using L. major [7] or Leishmania amazonensis [8]. Other studies showed that lesion development caused by L. major [9,10] or L. amazonensis [11] infection was delayed and less severe in the absence of T/B cells. Soong et al showed that CD4 + T lymphocytes are indispensable for pathogenesis during L. amazonensis infection [12].…”