Studies in the mouse model identify strain variability as a major determinant of disease outcome in Leishmania infantum infection

Marques, Filipe; Vale-Costa, Sílvia; Cruz, Tânia; Marques, Joana; Silva, Tânia; Neves, João V.; Cortes, Sofia; Fernandes, Ana; Rocha, Eduardo; Appelberg, Rui; Rodrigues, Pedro; Tomás, Ana M.; Gomes, Maria Salomé

doi:10.1186/s13071-015-1259-6

Cited by 9 publications

(6 citation statements)

References 42 publications

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“…Following the MRP physicochemical characterization, the formulation was tested on C57BL/6 mice model. Inbred mice, including C57BL/6 and BALB/c, have widely been used to assess early indications of microbicide safety profile and generally provide reproducible results. − Prior to any MRP exposure, the diestrus-like state of mice treated with Depo-Provera was assessed. Thus, the mice CVL were constantly collected, for up to 9 days, and analyzed for evidence of nucleated and cornified squamous epithelial cells and polymorph nuclear leukocytes.…”

Section: Resultsmentioning

confidence: 99%

Preclinical Safety Evaluation of HIV-1 gp120 Responsive Microbicide Delivery System in C57BL/6 Female Mice

et al. 2018

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Many novel vaginal/rectal microbicide formulations failed clinically due to safety concerns, indicating the need for the early investigation of lead microbicide formulations. In this study, the preclinical safety of an HIV-1 gp120 and mannose responsive microbicide delivery system (MRP) is evaluated in C57BL/6 mice. MRP was engineered through the layer-by-layer coating of calcium carbonate (CaCO3) with Canavalia ensiformis lectin (Con A) and glycogen. MRP mean particle diameter and zeta potential were 857.8 ± 93.1 nm and 2.37 ± 4.12 mV, respectively. Tenofovir (TFV) encapsulation and loading efficiencies in MRP were 70.1% and 16.3% w/w, respectively. When exposed to HIV-1 rgp120 (25 μg/mL), MRP released a significant amount of TFV (∼5-fold higher) in vaginal and seminal fluid mixture compared to the control (pre-exposure) level (∼59 μg/mL) in vaginal fluid alone. Unlike the positive control treated groups (e.g., nonoxynol-9), no significant histological damages and CD45+ cells infiltration were observed in the vaginal and major reproductive organ epithelial layers. This was probably due to MRP biocompatibility and its isosmolality (304.33 ± 0.58 mOsm/kg). Furthermore, compared to negative controls, there was no statistically significant increase in pro-inflammatory cytokines such as IL1α, Ilβ, IL7, IP10, and TNFα. Collectively, these data suggest that MRP is a relatively safe nanotemplate for HIV-1 gp120 stimuli responsive vaginal microbicide delivery system.

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Section: Resultsmentioning

confidence: 99%

Preclinical Safety Evaluation of HIV-1 gp120 Responsive Microbicide Delivery System in C57BL/6 Female Mice

et al. 2018

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“…Interestingly, although infected spleen cells produced more NO than uninfected ones, both the LIC and LII strains were still able to survive and multiply within the host, increasing parasite load at 60 dpi, especially in the case of the LII strain. Marques and collaborators (2015) [ 36 ] have reported that LII parasites were able to survive high amounts of NO added to the culture. Regarding ARG activity, lower urea production was observed in the spleen and liver of infected animals when compared to uninfected controls.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of biological aspects of Leishmania infantum strains

et al. 2020

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Leishmania infantum infantum (LII) is one of the species that causes visceral leishmaniasis (VL) in the Old World, while L. infantum chagasi (LIC) is present in the New World. Few studies address biological differences or the behavior of these strains during infection. These parasites live inside cells of their hosts, continuously evading microbicidal mechanisms and modulating the immune responses of these cells. One of the mechanisms used by these protozoa involves the L-arginine metabolism. Understanding the differences between Leishmania species and establishing an improved murine model for study of leishmaniasis are matters of extreme importance. Thereby, the objectives of this work were to analyze the biological and molecular differences between two Leishmania infantum strains (LII and LIC) and the degree of susceptibility to infection of mice with different genetic backgrounds. The infectivity in vivo and in vitro of LII and LIC strains was evaluated in BALB/c and Swiss Webster mice, as well the NOS and ARG activities. The LII strain was more infective than the LIC strain both in vivo and in vitro. In animals infected by the LII and LIC strains, differences in NOS and ARG activities occurred. In vitro, promastigotes of LII isolated from BALB/c and Swiss Webster mice showed higher ARG activity than LIC promastigotes during the growth curve. However, no difference was observed in intracellular NO production by promastigotes of these strains. The ARG gene sequences were compared, and those of both strains were identical. However, despite the similarity, the strains showed different expression levels of this gene. It can be concluded that although L. chagasi strains are considered identical to L. infantum strains from a molecular point of view, these strains have different biological behavior.

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“…Interestingly, although infected spleen cells produced NO more than uninfected ones, both LIC and LII were still able to survive and multiply within the host, increasing parasite load at 60 dpi, especially in the case of LII. Marques and collaborators (2015) [34] have reported that LII parasites were able to survive high amounts of NO added to the culture.…”

Section: Discussionmentioning

confidence: 99%

“…As published studies have shown that isolates of L. infantum belonging to the same zymodeme, which may present different sensitivities to the host’s immune response, which may be related to parasite virulence factors [27] . There are studies indicating that differences in infectivity between L. infantum strains could be related to modulation by the parasites of the expression of L-arginine metabolic enzymes during mouse infection [34] . Studies about differences between parasites from different geographic regions are needed.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of biological aspects ofLeishmania infantumisolates

Ferreira-Paes

Charret

Ribeiro

et al. 2020

Preprint

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17Leishmania infantum infantum (LII) is one of the species that causes visceral 18 leishmaniasis (VL) in the Old World, while L. infantum chagasi (LIC), and is present 19 in the New World. Few studies address the biological differences, as well as the 20 behaviour of these strains during infection. These parasites live inside the cells of 21 their hosts, continuously evading the microbicidal mechanisms and modulating the 22 immune response of these cells. One of the mechanisms used by these protozoa 23 involves the L-arginine metabolism. Given the importance of the understanding of 2 24 differences between Leishmania species, as well as establishing a better murine 25 model to study leishmaniases, the objectives of this work were to analyse the 26 biological and molecular differences between two Leishmania infantum strains (LII 27 and LIC) and the degree of susceptibility of mice with different genetic backgrounds 28 to infection, as well as to understand the role of arginase (ARG)/nitric oxide synthase 29 (NOS) in the parasite-host relationship. The infectivity in vivo and in vitro of LII and 30 LIC was performed in BALB/c and Swiss Webster mice, as well the NOS and ARG 31 activities. The LII strain showed more infective than the LIC strain both in vivo and 32 in vitro. In animals infected by both strains, a difference in NOS and ARG activities 33 occurred. In vitro, promastigotes of LII isolated from BALB/c and Swiss Webster mice 34 showed higher ARG activity than the LIC during the growth curve, however, no 35 difference was observed in intracellular NO production by promastigotes between 36 these strains. A comparison of the sequences of the ARG gene was made and both 37 strains were identical. However, despite the similarity, the strains showed different 38 expression of this gene. It can be concluded that although L. chagasi strains are 39 considered identical to L. infantum strains, both have different biological behaviour. 40 41 Keywords: Leishmania species, L-arginine, arginase, nitric oxide synthase 42 43 3 47 attributed to them, which can manifest in various forms with different symptoms 48 depending on the infecting species and the host immune response. The main forms 49 of the disease are cutaneous, mucocutaneous and visceral leishmaniases (VL), the 50 latter being the most lethal manifestation with almost 0.5 million new cases each 51year, if not treated the mortality rate can reach 100% in two years [1,2] . 52Leishmania infantum is one of the species that causes VL and is present in 53 the Mediterranean Basin, as well as in the Middle East and South Asia. Some years 54 ago, L. chagasi was considered a new species of Leishmania causing visceral 55 leishmaniasis in the New World. However, after genetic sequencing studies, 56L. chagasi was considered identical to L. infantum, being denominated L. infantum 57 (syn. L. chagasi) [3] . Nevertheless, further studies showing antigenic differences 58 between both strains, they have considered as two subspecies L. infantum infantum 59 in the Old Wor...

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Studies in the mouse model identify strain variability as a major determinant of disease outcome in Leishmania infantum infection

Cited by 9 publications

References 42 publications

Preclinical Safety Evaluation of HIV-1 gp120 Responsive Microbicide Delivery System in C57BL/6 Female Mice

Preclinical Safety Evaluation of HIV-1 gp120 Responsive Microbicide Delivery System in C57BL/6 Female Mice

Comparative analysis of biological aspects of Leishmania infantum strains

Comparative analysis of biological aspects ofLeishmania infantumisolates

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