Biology subjects

Chaves, M. M.

Publications and source records attributed to Chaves, M. M..

3 recordsLinked to original sources

bioRxiv2026

NLRP3 inflammasome signaling orchestrates hepatic granuloma organization and protective immunity

Granulomas are organized immune structures that contribute to host defense against persistent pathogens, yet the mechanisms that coordinate their assembly and protective function remain incompletely understood. Here, using experimental visceral leishmaniasis caused by Leishmania infantum and samples from patients with active disease, we identify the NLRP3 inflammasome as a regulator of protective hepatic granulomatous immunity. Inflammasome-associated mediators were elevated in patients and correlated with systemic inflammation. In mice, L. infantum induced NLRP3 inflammasome activation within hepatic granulomas, while single-cell and spatial transcriptomic analyses revealed enrichment of inflammasome-associated transcription in hepatic macrophages and granuloma-associated regions. NLRP3 deficiency did not prevent granuloma initiation but impaired granuloma expansion, cellular organization, and leukocyte accumulation. This response required Caspase-1/11 and IL-18, but was independent of IL-1{beta}. Loss of NLRP3 also impaired parasite control despite reducing hepatic inflammation and histopathological alterations. Together, our findings identify NLRP3-Caspase-1/11-IL-18 signaling as a mechanism that coordinates the cellular and spatial organization of protective hepatic granulomas, revealing granuloma architecture as a previously unrecognized function of inflammasome-mediated immunity and providing mechanistic insight into host resistance in visceral leishmaniasis, a potentially fatal neglected tropical disease.

immunology↗

bioRxiv2025

Exposure time to moderately high temperature affects photosynthetic response to water deficit in Eucalyptus globulus Labill.

The co-occurrence of drought and heat stress in the field is especially frequent and the plant response to a combination of these abiotic stresses is singular, remaining largely unknown. Understanding physiological responses to a combined stress is of particular importance in face of the imminent global climate changes, which is predicted to entail not only higher temperatures, but also increase in drought, imposing restrictions to the productivity of economically important species as E. globulus. This forest species is critically affected by changes in temperature and water availability, since its high productivity implies in high rates of water use. In order to evaluate the photosynthetic responses of Eucalyptus globulus to these environmental conditions, young plants were grown at 25{degrees} C and 35{degrees} C under different irrigation regimes: full irrigation - FI, moderate drought - MD, and severe drought - SD. Plants grown at 25{degrees} C FI and MD were also subjected to a short-term exposure to 35{degrees} C. Several ecophysiological variables, derived mainly from leaf gas exchange and chlorophyll a fluorescence measurements, were compared in order to test the hypotheses that: i) E. globulus show different responses to short or long-term exposure to 35{degrees} C; ii) the effect of both stresses combined will not be simply the sum of each condition applied separately. Our results showed that plants respond differently to water deficit according to the thermal regime. The combination of water deficit and a long-term exposure to 35{degrees} C caused a down-acclimation of the photosynthetic capacity, while plants under the short-term treatment showed a higher performance, even when compared to the 25{degrees} C control condition, supporting the hypothesis i. Thus, the short-term exposure to 35{degrees} C induced an increase in tolerance to water deficit. Since the response to a combination of heat and drought differed from the superposition of individual responses, as observed mainly at 35{degrees} C, the hypothesis ii was also supported by our results.

plant biology↗

bioRxiv2020

The role of dermis resident macrophages and their interaction with neutrophils in the early establishment of Leishmania major infection transmitted by sand fly bite

There is substantial experimental evidence to indicate that Leishmania infections that are transmitted naturally by the bites of infected sand flies differ in fundamental ways from the inflammatory and immune reactions initiated by needle inocula. We have used flow cytometry and intravital microscopy (IVM) to reveal the heterogeneity of sand fly transmission sites with respect to the subsets of phagocytes in the skin that harbor L. major within the first hours and days after infection. By flow cytometry analysis, dermis resident macrophages (TRMs) were on average the predominant infected cell type at 1 hr and 24 hr. By confocal IVM, the co-localization of L. major and neutrophils varied depending on the proximity of deposited parasites to the presumed site of vascular damage, defined by the highly localized swarming of neutrophils. Some of the dermal TRMs could be visualized acquiring their infections via transfer from or efferocytosis of parasitized neutrophils, providing direct evidence for the "Trojan Horse" model. The role of neutrophil engulfment by dermal TRMs and the involvement of the Tyro3/Axl/Mertk family of receptor tyrosine kinases in these interactions and in sustaining the anti-inflammatory program of dermal TRMs was supported by the effects observed in neutrophil depleted and in Axl-/-Mertk-/- mice. The Axl-/-Mertk-/- mice also displayed reduced parasite burdens but more severe pathology following L. major infection transmitted by sand fly bite. SummarySand flies transmit Leishmania major which causes cutaneous leishmaniasis in humans and in non-human hosts. Our analyses of sand fly transmission sites of L. major in the mouse skin revealed that dermis resident macrophages (TRM) were the predominant phagocytes to take up the parasite within the first 24 hr post-bite. The early involvement of neutrophils varied depending on the proximity of deposited parasites to the site of tissue damage around which the neutrophils coalesced. By intra-vital microscopy, some of the dermal TRMs could be visualized acquiring their infections by direct transfer from or phagocytosis of parasitized neutrophils. The involvement of the Tyro3/Axl/Mertk family of receptor tyrosine kinases in these cellular interactions and in sustaining the anti-inflammatory functions of dermal TRMs was supported by the reduced parasite burdens but more severe pathology observed in Axl-/-Mertk-/- mice. The heterogeneity of sand fly transmission sites with respect to the dose of parasites and the early cellular interactions described here likely contribute to the wide range of infection outcomes that are associated with natural transmission of L. major observed in mouse models and possibly humans.

immunology↗