Early Transcriptional Liver Signatures in Experimental Visceral Leishmaniasis

Abstract

Transcriptional analysis of complex biological scenarios has been used extensively, even though sometimes the results of such analysis may prove imprecise or difficult to interpret due to an overwhelming amount of information. In this study, a large-scale real-time qPCR experiment was coupled to multivariate statistical analysis in order to describe the main immunological events underlying the early L. infantum infection in livers of BALB/c mice. High-throughput qPCR was used to evaluate the expression of 223 genes related to immunological response and metabolism 1, 3, 5, and 10 days post infection. This integrative analysis showed strikingly different gene signatures at 1 and 10 days post infection, revealing the progression of infection in the experimental model based on the upregulation of particular immunological response patterns and mediators. The gene signature 1 day post infection was not only characterized by the upregulation of mediators involved in interferon signaling and cell chemotaxis, but also the upregulation of some inhibitory markers. In contrast, at 10 days post infection, the upregulation of many inflammatory and Th1 markers characterized a more defined gene signature with the upregulation of mediators in the IL-12 signaling pathway. Our results reveal a significant connection between the expression of innate immune response and metabolic and inhibitory markers in early L. infantum infection of the liver.

miR-548d-3p Is Up-Regulated in Human Visceral Leishmaniasis and Suppresses Parasite Growth in Macrophages

“…Among factors leading to the development of active disease, an immunosuppressive state resulting from either protein-energy malnutrition ( Malafaia, 2009 ) or HIV infection ( Lindoso et al., 2014 ) rank highest. However, participation of other factors gains evidence, including lipoprotein and lipoprotein fraction levels ( Carvalho et al., 2014 ) and growth factors ( Reis et al., 2021 ), and inhibition of secretion of pro-inflammatory cytokines and chemokines ( Tasew et al., 2021 ), along with alterations in the adaptive immune response ( Saporito et al., 2013 ; Palacios et al., 2021 ).…”

Editorial: Immunology and immunopathogenesis of human leishmaniasis

“…Human VL is characterized by depressed cellmediated immunity and decreased Th1 immune response (Carvalho et al, 1989;Bacellar et al, 2000). Also, VL is associated with increased production of multiple proinflammatory cytokines and chemokines (Saporito et al, 2013;Palacios et al, 2021;Tasew et al, 2021).…”

“…Human VL is characterized by depressed cellmediated immunity and decreased Th1 immune response (Carvalho et al, 1989;Bacellar et al, 2000). Also, VL is associated with increased production of multiple proinflammatory cytokines and chemokines (Saporito et al, 2013;Palacios et al, 2021;Tasew et al, 2021).Human CL caused by Leishmania braziliensis is characterized by an exacerbated cellular immune response and scarce numbers of parasites in the lesions (Bittencourt and Barral, 1991;Saldanha et al, 2017). The presence of pro-inflammatory cytokines, such as Frontiers in Cellular and Infection Microbiology frontiersin.org 01…”

Gene Expression Profiling of Classically Activated Macrophages in Leishmania infantum Infection: Response to Metabolic Pre-Stimulus with Itaconic Acid

“…The Irg1 gene has been described to be upregulated in tissue infected with L. infantum [ 18 , 19 ]. Considering that itaconate and Irg1 are upregulated during macrophage activation, we investigated the consequences of exogenous itaconate exposure prior to macrophage activation in Leishmania infantum infection: if ACOD1 catalyzes the upregulation of itaconate, how would an excess of itaconate affect the infection process?…”

“…The expression of some M1 markers at different timepoints during mouse liver infection by L. infantum has been described [ 18 ], but a large-scale transcriptional profile of the activation process of infected macrophages remains unexplored. For this purpose, murine bone marrow-derived macrophages (BMDMs) were differentiated ex vivo and subjected to IFNG stimulus and infection by L. infantum to obtain classically activated macrophages.…”