Leishmania major telomerase RNA knockout: From altered cell proliferation to decreased parasite infectivity.

This study focuses on the biological impacts of deleting the telomerase RNA from Leishmania major (LeishTER), a parasite responsible for causing leishmaniases, for which no effective treatment or prevention is available. TER is a critical player in the telomerase ribonucleoprotein complex, containing the template sequence copied by the reverse transcriptase component during telomere elongation. The success of knocking out both LeishTER alleles was confirmed, and no off-targets were detected. LmTER-/- cells share similar characteristics with other TER-depleted eukaryotes, such as altered growth patterns and partial G0/G1 cell cycle arrest in early passages, telomere shortening, and elevated TERRA expression. They also exhibit increased γH2A phosphorylation, suggesting that the loss of LeishTER induces DNA damage signaling. Moreover, pro-survival autophagic signals and mitochondrion alterations were shown without any detectable plasma membrane modifications. LmTER-/- retained the ability to transform into metacyclics, but their infectivity capacity was compromised. Furthermore, the overexpression of LeishTER was also deleterious, inducing a dominant negative effect that led to telomere shortening and growth impairments. These findings highlight TER's vital role in parasite homeostasis, opening discussions about its potential as a drug target candidate against Leishmania.

Aspectos evolutivos dos fenômenos imunopatológicos com ênfase na COVID-19 / Evolutionary aspects of immunopathological phenomena with emphasis on COVID-19

A seleção natural é o principal mecanismo da evolução das espécies, e favorece fenótipos com defesas imunes efetivas contra patógenos. Entretanto, há uma grande variação das respostas imunes entre os indivíduos da espécie humana e a ocorrência de fenômenos imunopatológicos. A infecção com o vírus da família Coronaviridae, SARS-CoV-2, responsável pela doença conhecida como COVID-19, induz a respostas imunes inflamatórias exacerbadas e à tempestade de citocinas, nos casos graves. Nesta revisão discutiremos, à luz da Evolução, esse aparente paradoxo entre as respostas imunes, e os três principais fatores que contribuem para a manutenção dos fenótipos hiperativos: o custo-benefício das respostas imunes, a coevolução e a história de vida da espécie.

Natural selection is the main mechanism by which species evolve, and it favors phenotypes associated with an effective immune defense against pathogens. However, human immune responses and the occurrence of immunopathological phenomena vary considerably from individual to individual. Infection with SARSCoV- 2, a virus of the Coronaviridae family causing the disease known as COVID-19, induces exacerbated inflammatory immune responses and cytokine storm in severe cases. In this review, we discuss, in the light of Evolution, this apparent paradox between the immune responses and the 3 main factors contributing to the maintenance of hyperactive phenotypes: the cost-effectiveness of immune responses, coevolution, and the life history of the species.

Granulomas in parasitic diseases: the good and the bad.

Parasitic diseases affect more than one billion people worldwide, and most of them are chronic conditions in which the treatment and prevention are difficult. The appearance of granulomas, defined as organized and compact structures of macrophages and other immune cells, during various parasitic diseases is frequent, since these structures will only form when individual immune cells do not control the invading agent. Th2-typering various parasitic diseases are frequent, since these structures will only form when individual immune cells do not control the invading agent. The characterization of granulomas in different parasitic diseases, as well as recent findings in this field, is discussed in this review, in order to understand the significance of the granuloma and its modulation in the host-parasite interaction and in the immune, pathological, and parasitological aspects of this interaction. The parasitic granulomatous diseases granulomatous amebic encephalitis, toxoplasmosis, leishmaniasis, neurocysticercosis, and schistosomiasis mansoni are discussed as well as the mechanistic and dynamical aspects of the infectious granulomas.

A cell-culturing system for the study of interaction between macrophages infected with leishmania amazonensis

The cell culture insert system is a culturing system for the study of contact-independent cellular communication. Leishmaniasis is a neglect tropical disease with no vaccines and the available drugs present toxic side effects. Studies on Leishmania interaction with host macrophages aim to develop strategies for parasite control and drug development. The purpose of this study was to evaluate the effects of interaction between non-infected and L. amazonensis-infected human macrophages, by using the cell culture system. The results showed that the infection index was reduced by 56.2% as compared to controls only when infected macrophages were inserted on both sides of the Transwell membranes. An improvement in macrophage viability was also observed in this cell culture. The levels of interleukin-1ß, an inflammatory cytokine, and nitric oxide, a microbicidal molecule, did not increase in L. amazonensis-infected macrophage cultures in the Transwell system; thus other soluble factors were responsible for parasite control