Early Suppression of Macrophage Gene Expression by Leishmania braziliensis

Sousa, Luana Guimaraes de; Andrade, Viviane M.; Bair, Thomas B.; Ettinger, Nicholas; Guimarães, Luana; Andrade, Laura Helena; Guimarães, Luiz Henrique; Machado, Paulo Roberto Lima; Carvalho, Edgar M.; Wilson, Mary E.; Schriefer, Albert

doi:10.3389/fmicb.2018.02464

Cited by 8 publications

(5 citation statements)

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“…Previous studies have demonstrated that signaling during L. amazonensis infection leads to the activation of MAPK1 and MAPK3 58 . MAPK14 has been poorly studied in the context of Leishmania infection, although downregulation of Mapk14 has previously been described to occur in L. braziliensis and L. major infections 41,60 . Most molecules from the recognition pathway were upregulated, indicating the activation of the downstream steps in recognition signaling cascades.…”

Section: Discussionmentioning

confidence: 99%

Differential immune response modulation in early Leishmania amazonensis infection of BALB/c and C57BL/6 macrophages based on transcriptome profiles

Aoki

Muxel

Zampieri

et al. 2019

Sci Rep

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The fate of Leishmania infection can be strongly influenced by the host genetic background. In this work, we describe gene expression modulation of the immune system based on dual global transcriptome profiles of bone marrow-derived macrophages (BMDMs) from BALB/c and C57BL/6 mice infected with Leishmania amazonensis. A total of 12,641 host transcripts were identified according to the alignment to the Mus musculus genome. Differentially expressed genes (DEGs) profiling revealed a differential modulation of the basal genetic background between the two hosts independent of L. amazonensis infection. In addition, in response to early L. amazonensis infection, 10 genes were modulated in infected BALB/c vs. non-infected BALB/c macrophages; and 127 genes were modulated in infected C57BL/6 vs. non-infected C57BL/6 macrophages. These modulated genes appeared to be related to the main immune response processes, such as recognition, antigen presentation, costimulation and proliferation. The distinct gene expression was correlated with the susceptibility and resistance to infection of each host. Furthermore, upon comparing the DEGs in BMDMs vs. peritoneal macrophages, we observed no differences in the gene expression patterns of Jun, Fcgr1 and Il1b, suggesting a similar activation trends of transcription factor binding, recognition and phagocytosis, as well as the proinflammatory cytokine production in response to early L. amazonensis infection. Analysis of the DEG profile of the parasite revealed only one DEG among the 8,282 transcripts, indicating that parasite gene expression in early infection does not depend on the host genetic background.

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Section: Discussionmentioning

confidence: 99%

Differential immune response modulation in early Leishmania amazonensis infection of BALB/c and C57BL/6 macrophages based on transcriptome profiles

Aoki

Muxel

Zampieri

et al. 2019

Sci Rep

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“…are strong promoters of cell-mediated immunity, mainly by induction of pro-inflammatory cytokines after in vivo infection. However, during intracellular infection of macrophages, the parasite initially suppresses the signal transduction pathways that lead to these pro-inflammatory responses ( 27 ). This likely reflects the parasite’s need to modulate immunity promptly, allowing it to multiply and survive in the host while avoiding excessive responses that could result in its elimination.…”

Section: Discussionmentioning

confidence: 99%

“…As a non-endemic site, these people were not tested for present or previous history of the disease; however, all of them reported verbally that they had never had leishmaniasis or had lived in an endemic site. Peripheral blood mononuclear cells (PBMCs) were obtained from heparinized blood using Ficoll Hypaque™ Plus density gradient (GE Healthcare, Biosciences AB Durham, NC, USA), as previously described ( 26 , 27 ). Briefly, cells were incubated in Teflon flasks for 6 days at 37°C and 5% CO2 to differentiate monocytes into macrophages.…”

Section: Methodsmentioning

confidence: 99%

MicroRNAs regulating macrophages infected with Leishmania L. (V.) Braziliensis isolated from different clinical forms of American tegumentary leishmaniasis

Lago,

Medina,

Lago

et al. 2023

Front. Immunol.

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BackgroundLeishmaniasis is an infectious disease caused by protozoa of the genus Leishmania. There are still no vaccines, and therapeutic options are limited, indicating the constant need to understand the fine mechanisms of its pathophysiology. An approach that has been explored in leishmaniasis is the participation of microRNAs (miRNAs), a class of small non-coding RNAs that act, in most cases, to repress gene expression. miRNAs play a role in the complex and plastic interaction between the host and pathogens, either as part of the host’s immune response to neutralize infection or as a molecular strategy employed by the pathogen to modulate host pathways to its own benefit.MethodsMonocyte-derived macrophages from healthy subjects were infected with isolates of three clinical forms of L. braziliensis: cutaneous (CL), mucosal (ML), and disseminated (DL) leishmaniasis. We compared the expression of miRNAs that take part in the TLR/NFkB pathways. Correlations with parasite load as well as immune parameters were analyzed.ResultsmiRNAs -103a-3p, -21-3p, 125a-3p -155-5p, -146a-5p, -132- 5p, and -147a were differentially expressed in the metastatic ML and DL forms, and there was a direct correlation between miRNAs -103a-3p, -21-3p, -155-5p, -146a-5p, -132-5p, and -9-3p and parasite load with ML and DL isolates. We also found a correlation between the expression of miR-21-3p and miR-146a-5p with the antiapoptotic gene BCL2 and the increase of viable cells, whereas miR-147a was indirectly correlated with CXCL-9 levels.ConclusionThe expression of miRNAs is strongly correlated with the parasite load and the inflammatory response, suggesting the participation of these molecules in the pathogenesis of the different clinical forms of L. braziliensis.

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“…L. (Viannia) braziliensis is the most spread parasite in Brazil, causing not only CL but also mucosal leishmaniasis (ML), a more severe clinical form of the disease. Clinical aspects variability indicate that, besides the genetic host background, antigenic strain differences of this Leishmania species also drive infection fates (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

A Cytokine Network Balance Influences the Fate of Leishmania (Viannia) braziliensis Infection in a Cutaneous Leishmaniasis Hamster Model

et al. 2021

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The golden hamster is a suitable model for studying cutaneous leishmaniasis (CL) due to Leishmania (Viannia) braziliensis. Immunopathological mechanisms are well established in the L. (L.) major-mouse model, in which IL-4 instructs a Th2 response towards progressive infection. In the present study, we evaluated the natural history of L. braziliensis infection from its first stages up to lesion establishment, with the aim of identifying immunological parameters associated with the disease outcome and parasitism fate. To this end, hamsters infected with 104, 105, or 106 promastigotes were monitored during the first hours (4h, 24h), early (15 days, 30 days) and late (50 days) post-infection (pi) phases. Cytokines, iNOS and arginase gene expression were quantified in the established lesions by reverse transcription-quantitative PCR. Compared to the 105 or 106 groups, 104 animals presented lower lesions sizes, less tissue damage, and lower IgG levels. Basal gene expression in normal skin was high for TGF-β, and intermediary for TNF, IL-6, and IL-4. At 4hpi, no cytokine induction was observed in the 104 group, while an upregulation of IL-6, IL-10, and IL-4 was observed in the 106 group. At 15dpi, lesion appearance was accompanied by an increased expression of all assessed cytokines, markedly in the 105 and 106 groups. Upregulation of all investigated cytokines was observed in the late phase, although less expressive in the 104 group. IFN-γ was the depending variable influencing tissue damage, while IL-6 was associated to parasite load. The network correlating gene expression and clinical and laboratorial parameters indicated inoculum-independent associations at 15 and 30dpi. A strong positive network correlation was observed in the 104 group, but not in the 105 or 106 groups. In conclusion, IL-4, IL-6, IL-10, and TGF-β are linked o L. braziliensis progression. However, a balanced cytokine network is the key for an immune response able to reduce the ongoing infection and reduce pathological damage.

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Early Suppression of Macrophage Gene Expression by Leishmania braziliensis

Cited by 8 publications

References 66 publications

Differential immune response modulation in early Leishmania amazonensis infection of BALB/c and C57BL/6 macrophages based on transcriptome profiles

Differential immune response modulation in early Leishmania amazonensis infection of BALB/c and C57BL/6 macrophages based on transcriptome profiles

MicroRNAs regulating macrophages infected with Leishmania L. (V.) Braziliensis isolated from different clinical forms of American tegumentary leishmaniasis

A Cytokine Network Balance Influences the Fate of Leishmania (Viannia) braziliensis Infection in a Cutaneous Leishmaniasis Hamster Model

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