Alterations in monocyte subsets and cytokine production after TLR activation in American Cutaneous Leishmaniasis

Abstract

Phenotypic and functional aspects of monocytes from Localized Cutaneous Leishmaniasis (LCL) patients were evaluated. The frequencies of monocyte subsets and TLR2/TLR4 expression were evaluated in fresh peripheral blood whereas cytokine production was evaluated in whole blood cell cultures stimulated with TLR agonists or Leishmania braziliensis antigen (Ag). CD16+ monocytes frequency was increased in patients compared with controls. A TLR4 agonist (LPS) induced expression of TNF and IL‐10 in monocyte subsets of patients and controls. The CD14+CD16+ monocytes expressed higher levels of these cytokines than CD14+CD16− cells. The levels of secreted TNF were higher in whole blood cell cultures from patients than controls after LPS/TLR4 or Ag stimulation. Whereas in controls there was a positive correlation between TNF and IL‐10 levels, this was not observed in stimulated cell cultures from patients. The high levels of LPS‐induced TNF were associated with the number of lesions and the percentages of CD14hiCD16+ monocytes. The levels of TLR2‐induced TNF were also associated with number of lesions. All monocyte subsets from patients expressed higher levels of TLR2 and TLR4 than controls. Data suggest that systemically activated monocytes contribute for an imbalance in pro‐ and anti‐inflammatory cytokine production during LCL, participating in the immunopathogenesis of the disease.

Blockade of TLR2 and TLR4 Attenuates Inflammatory Response and Parasite Load in Cutaneous Leishmaniasis

“…It follows that the identification of mechanisms capable of modulating this response may aid in the development of immunomodulatory therapies. The premise of our study was based on previous reports demonstrating that monocytes from CL patients express more TLR2 and TLR4 in association with elevated TNF production (16,32). The present results indicate that the neutralization of these receptors can indeed modulate the exacerbated inflammatory response documented in CL caused by L. braziliensis.…”

“…Moreover, the neutralization of TLR2 and TLR4 decreased TNF expression in monocytes after stimulation with SLA. These results seem to indicate that, in our in vivo experimental model, even after inducing infection and the partial clearance of parasites, the presence of SLA is able to continue stimulating the immune response by increasing the expression TLR2 and TLR4, in addition to the production of inflammatory molecules (32).…”

“…The CL group consisted of 20 males and 14 females with a median age of 45 years (range: . The control group was formed by 10 healthy subjects (HS) living in an urban area without exposure to L. braziliensis: 5 males and 5 females, median age 30 years (range: [22][23][24][25][26][27][28][29][30][31][32]. The present study received approval from the Institutional Review Board of the Professor Edgard Santos University Hospital Complex (HUPES-UFBA, protocol no.…”

The Effects of Polyhexamethylene Biguanide (PHMB) and TLR Agonists Alone or as Polyplex Nanoparticles against Leishmania infantum Promastigotes and Amastigotes

“…The contribution of TLR4 during Leishmania infection and treatment has been extensively studied, since it is considered to be important for efficient parasite control during innate immune responses [29,[52][53][54][55][56]. A previous study performed on whole blood of dogs stimulated with L. infantum antigen and different TLRa, demonstrated that TLR4a induced a potent pro-inflammatory cytokine stimulation [53].…”

Toll‐like receptor 10 controls TLR2‐induced cytokine production in monocytes from patients with Parkinson's disease

“…In homeostasis, in adult life, evidence shows that classical monocytes migrate into tissues, giving rise to resident macrophages with diverse functions according to tissues where they reside or remain as monocytes, which act as a peripheral reservoir of these cells, and non‐classical monocytes are considered patrolling cells searching for particles or endothelium injury in blood vessels (Canè et al., 2019; Guilliams et al., 2018; Patel et al., 2017). In inflammatory conditions, classical monocytes are considered inflammatory cells and migrate into injured tissues with high functional plasticity; however, among monocyte subsets, those expressing CD16 have been mostly detected in several inflammatory/infectious diseases, functioning as antigen‐presenting cells and potent producers of cytokines depending on the stimuli (Boyette et al., 2017; Cros et al., 2010; Guilliams et al., 2018; Quixabeira et al., 2019; Ziegler‐Heitbrock, 2007). The evaluation of monocytes in PD has demonstrated that these cells are hyperresponsive to inflammatory stimuli (Grozdanov et al., 2014).…”