The Involvement of TLR2 and TLR4 in Cytokine and Nitric Oxide Production in Visceral Leishmaniasis Patients before and after Treatment with Anti-Leishmanial Drugs

Gatto, Mariana; Abreu, Mariana Miziara de; Tasca, Karen Ingrid; Golim, Márjorie de Assis; Silva, Laura Denise Mendes da; Simão, José Cláudio; Fortaleza, Carlos Magno Castelo Branco; Soares, Ângela Maria Victoriano de Campos; Calvi, Sueli Aparecida

doi:10.1371/journal.pone.0117977

Cited by 23 publications

(22 citation statements)

References 85 publications

(95 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although TLR‐2 is deemed to alter production of NO, our data did not support a correlation with changes in expression of iNOS, in agreement with observations made in TLR‐2‐deficient mice . Of note, TNF‐α has also been previously suggested to modulate induction of iNOS, while IL‐10 was reported to have inhibitory effects on the production of the enzyme .…”

Section: Discussionsupporting

confidence: 78%

“…We found that TLR‐2 expression was positively correlated with TNF‐α and IL‐10. Gatto et al observed similar results in human patients with active visceral leishmaniosis. These results indicate that TLR‐2 could be regulating TNF‐α and IL‐10 in an attempt to combat infection.…”

Section: Discussionmentioning

confidence: 54%

“…16 Of note, TLR-2 can affect the production of the inducible nitric oxide synthase (iNOS) enzyme, which catalyses nitric oxide (NO) production. [17][18][19][20][21] Conversely, TLR-2-deficient mice infected with Leishmania donovani showed enhanced macrophage antileishmanial activity with no changes in the liver expression of iNOS as compared to wild-type mice. 22 Considering the importance of the skin in the transmission of parasites of the Leishmania genus, we aimed at evaluating the expression of the immune response genes TLR-2, iNOS, TNFα and IL-10 in the skin of dogs naturally affected by CanL and related them to the skin parasite load (PL).…”

Section: Introductionmentioning

confidence: 99%

“…In particular, increased expression of Toll‐like receptor 2 (TLR‐2) has been related to a lower parasite load in the skin of naturally infected dogs, as well as to reduced infectiousness to the vector . Of note, TLR‐2 can affect the production of the inducible nitric oxide synthase (iNOS) enzyme, which catalyses nitric oxide (NO) production . Conversely, TLR‐2‐deficient mice infected with Leishmania donovani showed enhanced macrophage antileishmanial activity with no changes in the liver expression of iNOS as compared to wild‐type mice …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dog skin parasite load, TLR‐2, IL‐10 and TNF‐α expression and infectiousness

Pereira-Fonseca

Oliveira-Rovai

Rodas

et al. 2017

Parasite Immunology

View full text Add to dashboard Cite

Visceral leishmaniosis is a zoonotic disease that is transmitted by Lutzomyia longipalpis sandflies. Dogs are the main peri-urban reservoir of the disease, and progression of canine leishmaniosis is dependent on the type of immune response elaborated against the parasite. Type 1 immunity is characterized by effective cellular response, with production of pro-inflammatory cytokines such as tumour necrosis factor alpha (TNF-α). In contrast, Type 2 immunity is predominantly humoral, associated with progression of the disease and mediated by anti-inflammatory cytokines such as interleukin 10 (IL-10). Although seemly important in the dynamics of leishmaniosis, other gene products such as toll-like receptor 2 (TRL-2) and inducible nitric oxide synthase (iNOS) exert unclear roles in the determination of the type of immune response. Given that the dog skin serves as a micro-environment for the multiplication of Leishmania spp., we investigated the parasite load and the expression of TLR-2, iNOS, IL-10 and TNF-α in the skin of 29 infected and 8 control dogs. We found that increased parasite load leads to upregulation of TLR-2, IL-10 and TNF-α, indicating that abundance of these transcripts is associated with infection. We also performed a xenodiagnosis to demonstrate that increased parasitism is a risk factor for infectiousness to sandflies.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dog skin parasite load, TLR‐2, IL‐10 and TNF‐α expression and infectiousness

Pereira-Fonseca

Oliveira-Rovai

Rodas

et al. 2017

Parasite Immunology

View full text Add to dashboard Cite

show abstract

“…Additionally, the levels of TNF-α, IL-10, and TGF-β increased, and those of IFN-γ, IL-17, and NO decreased. Although the expression of these two receptors did not change in lymphocytes after treatment, in monocytes they were found to be lower for TNF-α and IL-10 and higher for TGF-β, IFN-γ, IL-17, and NO [101].…”

Section: Tlrs In the Outcome Of Disease 71 Leishmaniasismentioning

confidence: 71%

TLR-Mediated Host Immune Response to Parasitic Infectious Diseases

Aguirre-Garcı́a¹,

Rojas-Bernabé²,

Gómez-García³

et al. 2020

Toll-Like Receptors

View full text Add to dashboard Cite

Toll-like receptors (TLRs) are important for the host immune response to a variety of pathogens, including bacteria, viruses, fungi, and parasites. These receptors become activated upon recognizing pathogen-associated molecular patterns (PAMPs) and thus initiate the innate immune response to the corresponding pathogen. A key aspect of TLRs is their activation of signaling that leads to cytokine production and an inflammatory response. Additionally, TLRs act as the bridge between innate and acquired immunity, enhancing phagocytosis and the process of killing parasites. We herein focus on how parasites (protozoans and helminths) and their derived products have the capability of stimulating or evading the host response by triggering or inhibiting TLR activation. Parasites often develop successful survival strategies that imply interference with the host immune response. Accordingly, many of these organisms have molecules that modulate inflammation and other aspects of host immunity. Taking advantage of such mechanisms, there are some anti-inflammatory therapies based on human infection with helminths. Helminths and protozoans influence the activity of various TLRs, especially TLR2, TLR4, and TLR9. A better understanding of the role of TLRs and their parasite-derived ligands should certainly provide new therapeutic tools for combatting various parasitic and inflammatory diseases.

show abstract

Neutrophils and Visceral Leishmaniasis: Impact on innate immune response and cross‐talks with macrophages and dendritic cells

Kupani

Pandey²,

Mehrotra

2020

Journal Cellular Physiology

View full text Add to dashboard Cite

Neutrophils with their array of microbicidal activities are the first innate immune cells to guard against infection. They are also most crucial for the host's initial defense against Leishmania parasites which cause clinically diverse diseases ranging from self‐healing cutaneous leishmaniasis (CL) to a more severe visceral form, visceral leishmaniasis (VL). Neutrophils are recruited in large numbers at the infection site after bite of sandfly, which is the vector for the disease. The initial interaction of neutrophils with the parasites may modulate the subsequent innate and adaptive immune responses and hence affect the disease outcome. The purpose of this review is to comprehensively appraise the role of neutrophils during the early stages of Leishmania infection with a focus on the visceral form of the disease. In the past decade, new insights regarding the role of neutrophils in VL have surfaced which have been extensively elaborated in the present review. In addition, since much of the information regarding neutrophil–Leishmania early interaction has accumulated through studies on mouse models of CL, these studies are also revisited. We begin by reviewing the factors which drive the recruitment of neutrophils at the site of injection by the sandfly. We then discuss the studies delineating the molecular mechanisms involved in the uptake of the Leishmania parasite by neutrophils and how the parasite subverts their microbicidal functions. In the end, the interaction of infected neutrophils with macrophages and dendritic cells is summarized.

show abstract

The Involvement of TLR2 and TLR4 in Cytokine and Nitric Oxide Production in Visceral Leishmaniasis Patients before and after Treatment with Anti-Leishmanial Drugs

Cited by 23 publications

References 85 publications

Dog skin parasite load, TLR‐2, IL‐10 and TNF‐α expression and infectiousness

Dog skin parasite load, TLR‐2, IL‐10 and TNF‐α expression and infectiousness

TLR-Mediated Host Immune Response to Parasitic Infectious Diseases

Neutrophils and Visceral Leishmaniasis: Impact on innate immune response and cross‐talks with macrophages and dendritic cells

Contact Info

Product

Resources

About