Infection with Leishmania major Induces a Cellular Stress Response in Macrophages

Filardy, Alessandra A.; Silva, Ana Caroline Costa da; Koeller, Carolina M.; Guimarães-Pinto, Kamila; Ribeiro-Gomes, Flávia L.; Lopes, Marcela F.; Heise, Norton; Freire-de-Lima, Célio Geraldo; Nunes, Marise P.; DosReis, George A.

doi:10.1371/journal.pone.0085715

Cited by 38 publications

(26 citation statements)

References 47 publications

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“…Since JNK is a key component of innate immunity pathways of many animals, this is not surprising: many bacteria, viruses, and eukaryotic parasites directly "tamper with" the JNK pathway in order to evade, suppress, or modify immune responses to their advantage (440,443,444). Enzymes produced by pathogenic bacteria and injected into the host cells, in most cases by a type III secretion system, are among the best examples (reviewed in references 445 and 446).…”

Section: Microbial Pathogens Affecting Jnk Signalingmentioning

confidence: 99%

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

Zeke

Misheva

Reményi

et al. 2016

Microbiol Mol Biol Rev

386

350

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SUMMARYThe c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states.

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Section: Microbial Pathogens Affecting Jnk Signalingmentioning

confidence: 99%

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

Zeke

Misheva

Reményi

et al. 2016

Microbiol Mol Biol Rev

386

350

View full text Add to dashboard Cite

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“…Leishmania has evolved complex strategies to establish infection and survive within macrophages, counteracting macrophage defenses such as oxidative damage, immune activation, antigen presentation and apoptosis, at the same time improving nutrient availability [ 79 ]. Recently, the cellular responses induced by infection with Leishmania major in macrophages from resistant C57BL/6 mice has been investigated, evidencing an inflammatory response, mediated by ROS and JNK signaling, triggered by a stress stimulus provided by the parasite [ 80 ]. However, the role of UPR in infected cells remains poorly investigated.…”

Section: The Upr In Parasitized Cellsmentioning

confidence: 99%

Endoplasmic Reticulum Stress and Unfolded Protein Response in Infection By Intracellular Parasites

2017

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Perturbations of the physiological status of the endoplasmic reticulum (ER) trigger a specific response known as the ER stress response or unfolded protein response (UPR). In mammalian cells, the UPR is mediated by three ER transmembrane proteins (IRE1, PERK and ATF6) which activate three signaling cascades to restore ER homeostasis. In recent years, a cross-talk between UPR, inflammatory and microbial sensing pathways has been elucidated. Pathogen infection can lead to UPR activation; moreover, several pathogens subvert the UPR to promote their survival and replication. While the UPR in viral and bacterial infection has been characterized, little is known about the role of UPR in intracellular parasite infection. Here, we review recent findings on UPR induction/modulation by intracellular parasites in host cells.

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“…Interestingly, some cytokines such as IL-28A (IFN-λ2), IL-28B (IFN-λ3) in mice and humans, and IL-29 (IFN-λ3) in humans could harness the production of IL-1β. Hence, this cytokine could not be detected in Leishmania lesions, which were either in the shrinkage or healing periods (35,36).…”

Section: Group Control (Treated With Pbs)mentioning

confidence: 87%

Comparison of Proinflammatory Gene Expression in Lesions Caused by either Burn Injuries or Cutaneous Leishmaniasis

et al. 2016

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Background: Leishmaniasis is a worldwide disease prevalent in tropical and subtropical countries in the world. Characterization of inflammatory responses produced in cutaneous Leishmaniasis has not yet been completed. The current study aims to assess and compare pro-inflammatory cytokines between burning injuries and Leishmania infection. Methods: the specific primers were designed for 10 proinflammatory genes including CCL4, CCL3, TNF-α, IL-1α, IL-12P35, IL-12P40, CCL5, CCR5, IL-1β, and IFNγ. Their expressions were assessed and compared using RT-PCR in the lesions caused by either Leishmania or burning in BALB/c mice. Results: None of the proinflammatory genes were expressed in the healthy tissue and in the lesions caused by Leishmania, except IFNγ. The other genes were down-regulated by the parasite in untreated mice. In mice treated with Glucantime, the expression of the proinflammatory genes restarted. In contrast, the figure of expression of proinflammatory genes in lesions caused by burning was different. The proinflammatory genes were expressed in untreated lesions and down regulated in cured lesions. Conclusions: The findings of the current study indicated a role for Leishmania in suppression of proinflammatory genes and a role of proinflammatory genes in healing of burning lesions.

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Infection with Leishmania major Induces a Cellular Stress Response in Macrophages

Cited by 38 publications

References 47 publications

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

Endoplasmic Reticulum Stress and Unfolded Protein Response in Infection By Intracellular Parasites

Comparison of Proinflammatory Gene Expression in Lesions Caused by either Burn Injuries or Cutaneous Leishmaniasis

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