Leishmania infantum antigens modulate memory cell subsets of liver resident T lymphocyte

Rodrigues, A.; Claro, M.; Alexandre‐Pires, Graça; Santos-Mateus, David; Martins, Catarina; Valério-Bolas, Ana; Rafael-Fernandes, Mariana; Pereira, Maria A.; Fonseca, Isabel Pereira da; Tomás, Ana M.; Santos‐Gomes, Gabriela

doi:10.1016/j.imbio.2016.08.009

Cited by 13 publications

(18 citation statements)

References 28 publications

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“…These results are in accordance with those of other authors who detected parasites in all spleen and liver samples at week 6 after infection (14,17). Our results revealed that the initial commitment of the strain is to the liver, and over the course of the infection the parasite disseminates to the spleen, corroborating with the fact that the liver is the compartment of acute resolving infections, whereas the spleen is the compartment of parasite persistence (18).…”

Section: Discussionsupporting

confidence: 93%

Mixed Formulation of Conventional and Pegylated Meglumine Antimoniate-Containing Liposomes Reduces Inflammatory Process and Parasite Burden in Leishmania infantum-Infected BALB/c Mice

Reis

Brito

Cardoso

et al. 2017

Antimicrob Agents Chemother

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Pentavalent antimonial has been the first choice treatment for visceral leishmaniasis; however, it has several side effects that leads to low adherence to treatment. Liposome-encapsulated meglumine antimoniate (MA) arises as an important strategy for chemotherapy enhancement. We evaluated the immunopathological changes using the mixture of conventional and pegylated liposomes with MA. The mice were infected with and a single-dose treatment regimen. Comparison was made with groups treated with saline, empty liposomes, free MA, and a liposomal formulation of MA (Lipo MA). Histopathological analyses demonstrated that animals treated with Lipo MA showed a significant decrease in the inflammatory process and the absence of granulomas. The stimulation of splenocytes showed a significant increase of gamma interferon (IFN-γ) produced by CD8 T cells and a decrease in interleukin-10 (IL-10) produced by CD4 and CD8 T cells in the Lipo MA. Furthermore, the Lipo MA group showed an increase in the IFN-γ/IL-10 ratio in both CD4 and CD8 T cell subsets. According to the parasite load evaluation using quantitative PCR, the Lipo MA group showed no DNA in the spleen (0.0%) and 41.4% in the liver. In addition, we detected a low positive correlation between parasitism and histopathology findings (inflammatory process and granuloma formation). Thus, our results confirmed that Lipo MA is a promising antileishmanial formulation able to reduce the inflammatory response and induce a type 1 immune response, accompanied by a significant reduction of the parasite burden into hepatic and splenic compartments in treated animals.

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Section: Discussionsupporting

confidence: 93%

Mixed Formulation of Conventional and Pegylated Meglumine Antimoniate-Containing Liposomes Reduces Inflammatory Process and Parasite Burden in Leishmania infantum-Infected BALB/c Mice

Reis

Brito

Cardoso

et al. 2017

Antimicrob Agents Chemother

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“…To date, several vaccine candidates against the different types of leishmaniasis have been proposed and with promising results in murine models, but none of them have achieved the market for human immunization and VL prevention. This may be due to issues related to the different levels of immune memory generation that are currently agreed upon the guidelines for vaccine development in different research groups [ 6 , 52 , 58 , 59 ]. In our study, we characterized memory T cell phenotype in the spleen of the immunized animals.…”

Section: Discussionmentioning

confidence: 99%

Chimeric Vaccines Designed by Immunoinformatics-Activated Polyfunctional and Memory T Cells That Trigger Protection against Experimental Visceral Leishmaniasis

et al. 2020

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Many vaccine candidates against visceral leishmaniasis (VL) have been proposed; however, to date, none of them have been efficacious for the human or canine disease. On this basis, the design of leishmaniasis vaccines has been constantly changing, and the use of approaches to select specific epitopes seems to be crucial in this scenario. The ability to predict T cell-specific epitopes makes immunoinformatics an even more necessary approach, as in VL an efficient immune response against the parasite is triggered by T lymphocytes in response to Leishmania spp. immunogenic antigens. Moreover, the success of vaccines depends on the capacity to generate long-lasting memory and polyfunctional cells that are able to eliminate the parasite. In this sense, our study used a combination of different approaches to develop potential chimera candidate vaccines against VL. The first point was to identify the most immunogenic epitopes of Leishmania infantum proteins and construct chimeras composed of Major histocompatibility complex (MHC) class I and II epitopes. For this, we used immunoinformatics features. Following this, we validated these chimeras in a murine model in a thorough memory study and multifunctionality of T cells that contribute to a better elucidation of the immunological protective mechanisms of polyepitope vaccines (chimera A and B) using multicolor flow cytometry. Our results showed that in silico-designed chimeras can elicit polyfunctional T cells producing T helper (Th)1 cytokines, a strong immune response against Leishmania antigen, and the generation of central and effector memory T cells in the spleen cells of vaccinated animals that was able to reduce the parasite burden in this organ. These findings contribute two potential candidate vaccines against VL that can be used in further studies, and help in this complex field of vaccine development against this challenging parasite.

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“…Liver T RM have also been implicated in the immune response against Leishmania . The recombinant proteins LirCyp1 and LirSOD of L. infantum appear to be good candidates for promoting the expansion of liver memory T cells ( 184 ). No current vaccine exists for this potentially fatal disease.…”

Section: The Role Of T Rm In Parasitic (Protozoa Amentioning

confidence: 99%

A Systematic Review: The Role of Resident Memory T Cells in Infectious Diseases and Their Relevance for Vaccine Development

et al. 2018

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BackgroundResident memory T cells have emerged as key players in the immune response generated against a number of pathogens. Their ability to take residence in non-lymphoid peripheral tissues allows for the rapid deployment of secondary effector responses at the site of pathogen entry. This ability to provide enhanced regional immunity has gathered much attention, with the generation of resident memory T cells being the goal of many novel vaccines.ObjectivesThis review aimed to systematically analyze published literature investigating the role of resident memory T cells in human infectious diseases. Known effector responses mounted by these cells are summarized and key strategies that are potentially influential in the rational design of resident memory T cell inducing vaccines have also been highlighted.MethodsA Boolean search was applied to Medline, SCOPUS, and Web of Science. Studies that investigated the effector response generated by resident memory T cells and/or evaluated strategies for inducing these cells were included irrespective of published date. Studies must have utilized an established technique for identifying resident memory T cells such as T cell phenotyping.ResultsWhile over 600 publications were revealed by the search, 147 articles were eligible for inclusion. The reference lists of included articles were also screened for other eligible publications. This resulted in the inclusion of publications that studied resident memory T cells in the context of over 25 human pathogens. The vast majority of studies were conducted in mouse models and demonstrated that resident memory T cells mount protective immune responses.ConclusionAlthough the role resident memory T cells play in providing immunity varies depending on the pathogen and anatomical location they resided in, the evidence overall suggests that these cells are vital for the timely and optimal protection against a number of infectious diseases. The induction of resident memory T cells should be further investigated and seriously considered when designing new vaccines.

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Leishmania infantum antigens modulate memory cell subsets of liver resident T lymphocyte

Cited by 13 publications

References 28 publications

Mixed Formulation of Conventional and Pegylated Meglumine Antimoniate-Containing Liposomes Reduces Inflammatory Process and Parasite Burden in Leishmania infantum-Infected BALB/c Mice

Mixed Formulation of Conventional and Pegylated Meglumine Antimoniate-Containing Liposomes Reduces Inflammatory Process and Parasite Burden in Leishmania infantum-Infected BALB/c Mice

Chimeric Vaccines Designed by Immunoinformatics-Activated Polyfunctional and Memory T Cells That Trigger Protection against Experimental Visceral Leishmaniasis

A Systematic Review: The Role of Resident Memory T Cells in Infectious Diseases and Their Relevance for Vaccine Development

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