Low and high-dose intradermal infection with Leishmania majorand Leishmania amazonensis in C57BL/6 mice

Côrtes, Denise Fonseca; Carneiro, Mariângela; Santos, Liliane Martins dos; Souza, Talita Correia de Oliveira; Maioli, Tatiani Uceli; Duz, Ana Luiza Cassin; Ramos-Jorge, Maria Letícia; Afonso, Luís Carlos Crocco; Carneiro, Cláudia Martins; Vieira, Leda Quércia

doi:10.1590/s0074-02762010000600002

Cited by 28 publications

(22 citation statements)

References 39 publications

(45 reference statements)

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“…gp91 phox2/2 mice presented with significantly enhanced pathology compared with WT mice, including increased lesion size and complete loss of the ear by 16 wk p.i., despite equivalent parasite loads. Although infection-related pathology was more severe in gp91 phox2/2 mice, we ultimately observed progressive disease over time in both strains, confirming our previous observation that C57BL/6 mice are susceptible to infection with L. amazonensis following intradermal inoculation (3). Previously, we addressed the role of ROS from NOX2 in C57BL/6 mice following s.c. infection of the footpad with L. amazonensis (31) and found a limited role for gp91 phox in disease.…”

Section: Discussionsupporting

confidence: 88%

NOX2-Derived Reactive Oxygen Species Control Inflammation during Leishmania amazonensis Infection by Mediating Infection-Induced Neutrophil Apoptosis

Carneiro

Roma

Ranson

et al. 2018

The Journal of Immunology

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Reactive oxygen species (ROS) produced by NADPH phagocyte oxidase isoform (NOX2) are critical for the elimination of intracellular pathogens in many infections. Despite their importance, the role of ROS following infection with the eukaryotic pathogen has not been fully elucidated. We addressed therole of ROS in C57BL/6 mice following intradermal infection with Despite equivalent parasite loads compared with wild-type (WT) mice, mice deficient in ROS production by NOX2 due to the absence of the gp91 subunit (gp91) had significantly more severe pathology in the later stages of infection. Pathology in gp91 mice was not associated with alterations in CD4 T cell-mediated immunity but was preceded by enhanced neutrophil accumulation at the dermal infection site. Ex vivo analysis of infected versus uninfected neutrophils revealed a deficiency in infection-driven apoptosis in gp91 mice versus WT mice. gp91 mice presented with higher percentages of healthy or necrotic neutrophils but lower percentages of apoptotic neutrophils at early and chronic time points. In vitro infection of gp91 versus WT neutrophils also revealed reduced apoptosis and CD95 expression but increased necrosis in infected cells at 10 h postinfection. Provision of exogenous ROS in the form of HO reversed the necrotic phenotype and restored CD95 expression on infected gp91 neutrophils. Although ROS production is typically viewed as a proinflammatory event, our observations identify the importance of ROS in mediating appropriate neutrophil apoptosis and the importance of apoptosis in inflammation and pathology during chronic infection.

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Section: Discussionsupporting

confidence: 88%

NOX2-Derived Reactive Oxygen Species Control Inflammation during Leishmania amazonensis Infection by Mediating Infection-Induced Neutrophil Apoptosis

Carneiro

Roma

Ranson

et al. 2018

The Journal of Immunology

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“…In the chronic phase, despite the presence of a large lesion, it was not possible to detect parasites [ 45 ]. Others demonstrated that intradermal infection on ears of C57BL/6 mice using L amazonensis PH8 strain, isolated from sand flies, showed a progressive disease with a chronic lesion, in other words, in the chronic phase, the lesion was not uncontrolled; however, also did not heal [ 46 , 47 ]. The different site of infection (ear) or the different route of infection (intradermal) from subcutaneous injection in the hind paw could affect the lesion progression [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice

et al. 2016

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BackgroundWe have previously demonstrated that intranasal vaccination of highly susceptible BALB/c mice with whole Leishmania amazonensis antigens (LaAg) leads to protection against murine cutaneous leishmaniasis. Here, we evaluate the response of partially resistant C57BL/6 mice to vaccination as a more representative experimental model of human cutaneous leishmaniasis.MethodsC57BL/6 mice from different animal facilities were infected with L. amazonensis (Josefa strain) to establish the profile of infection. Intranasal vaccination was performed before the infection challenge with two doses of 10 μg of LaAg alone or associated with the adjuvant ADDAVAX® by instillation in the nostrils. The lesion progression was measured with a dial caliper and the parasite load by limited dilution assay in the acute and chronic phases of infection. Cytokines were quantified by ELISA in the homogenates of infected footpads.ResultsC57BL/6 mice from different animal facilities presented the same L. amazonensis infection profile, displaying a progressive acute phase followed by a controlled chronic phase. Parasites cultured in M199 and Schneider’s media were equally infective. Intranasal vaccination with LaAg led to milder acute and chronic phases of the disease. The mechanism of protection was associated with increased production of IFN-gamma in the infected tissue as measured in the acute phase. Association with the ADDAVAX® adjuvant did not improve the efficacy of intranasal LaAg vaccination. Rather, ADDAVAX® reduced vaccination efficacy.ConclusionThis study demonstrates that the efficacy of adjuvant-free intranasal vaccination with LaAg is extendable to the more resistant C57Bl/6 mouse model of infection with L. amazonensis, and is thus not exclusive to the susceptible BALB/c model. These results imply that mucosal immunomodulation by LaAg leads to peripheral protection irrespective of the genetic background of the host.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1822-9) contains supplementary material, which is available to authorized users.

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“…Histological damage was calculated from observation of 10 different fields (40× magnification) of H&E‐stained sections from each animal. The histopathological score grading system was evaluated by the degree of inflammation as described by Côrtes DF . The total score was defined as the sum of all scores.…”

Section: Methodsmentioning

confidence: 99%

Total Leishmania antigens with Poly(I:C) induce Th1 protective response

Sánchez

Eliçabe

Genaro

et al. 2017

Parasite Immunology

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Our proposal was to develop a vaccine based on total Leishmania antigens (TLA) adjuvanted with polyinosinic-polycytidylic acid [Poly(I:C)] able to induce a Th1 response which can provide protection against Leishmania infection. Mice were vaccinated with two doses of TLA-Poly(I:C) administered by subcutaneous route at 3-week interval. Humoral and cellular immune responses induced by the immunization were measured. The protective efficacy of the vaccine was evaluated by challenging mice with infective promastigotes of Leishmania (Leishmania) amazonensis into the footpad. Mice vaccinated with TLA-Poly(I:C) showed a high anti-Leishmania IgG titre, as well as increased IgG1 and IgG2a subclass titres compared with mice vaccinated with the TLA alone. The high IgG2a indicated a Th1 bias response induced by the TLA-Poly(I:C) immunization. Accordingly, the cellular immune response elicited by the formulation was characterized by an increased production of IFN-γ and no significant production of IL-4. The TLA-Poly(I:C) immunization elicited good protection, which was associated with decreased footpad swelling, a lower parasite load and a reduced histopathological alteration in the footpad. Our findings demonstrate a promising vaccine against cutaneous leishmaniasis that is relatively economic and easy to develop and which should be taken into account for preventing leishmaniasis in developing countries.

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Low and high-dose intradermal infection with Leishmania majorand Leishmania amazonensis in C57BL/6 mice

Abstract: A model of skin infection with Leishmania amazonensis with low doses of parasites is compared to infection

Cited by 28 publications

References 39 publications

NOX2-Derived Reactive Oxygen Species Control Inflammation during Leishmania amazonensis Infection by Mediating Infection-Induced Neutrophil Apoptosis

NOX2-Derived Reactive Oxygen Species Control Inflammation during Leishmania amazonensis Infection by Mediating Infection-Induced Neutrophil Apoptosis

Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice

Total Leishmania antigens with Poly(I:C) induce Th1 protective response

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