Transcription of innate immunity genes and cytokine secretion by canine macrophages resistant or susceptible to intracellular survival of Leishmania infantum

Turchetti, A; Costa, Lourena E.; Romão, Everton de Lima; Fujiwara, Ricardo Toshio; Paixão, Tatiane Alves da; Santos, Renato L.

doi:10.1016/j.vetimm.2014.11.010

Cited by 37 publications

(30 citation statements)

References 20 publications

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“…IFNγ expression is also a result of the activation of blood mononuclear cells in the dog (Panaro et al 2001) and increases the cytotoxic activity of canine alveolar macrophages in vitro (Kurzman et al 1999). Monocyte-derived canine macrophages secrete IFNγ when they kill the intracellular parasite Leishmania (Turchetti et al 2015). Taken together, these findings support the notion that the increased IL-6 and IFNγ expression of canine ATMs resembles the obesity-induced M1 macrophage activation in mice.…”

Section: Discussionsupporting

confidence: 67%

Adipose tissue macrophages in non-rodent mammals: a comparative study

et al. 2015

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The stromal vascular fraction (SVF) of adipose tissue in rodents and primates contains mesenchymal stem cells and immune cells. SVF cells have complex metabolic, immune and endocrine functions with biomedical impact. However, in other mammals, the amount of data on SVF stem cells is negligible and whether the SVF hosts immune cells is unknown. In this study, we show that the SVF is rich in immune cells, with a dominance of adipose tissue macrophages (ATMs) in cattle (Bos primigenius taurus), domestic goat (Capra aegagrus hircus), domestic sheep (Ovis aries), domestic cat (Felis catus) and domestic dog (Canis familiaris). ATMs of these species are granulated lysosome-rich cells with lamellipodial protrusions and express the lysosome markers acid phosphatase 5 (ACP-5) and Mac-3/Lamp-2. Using ACP-5 and Mac-3/Lamp-2 as markers, we additionally detected ATMs in other species, such as the domestic horse (Equus ferus caballus), wild boar (Sus scrofa) and red fox (Vulpes vulpes). Feline and canine ATMs also express the murine macrophage marker F4/80 antigen. In the lean condition, the alternative macrophage activation marker CD206 is expressed by feline and canine ATMs and arginase-1 by feline ATMs. Obesity is associated with interleukin-6 and interferon gamma expression and with overt tyrosine nitration in both feline and canine ATMs. This resembles the obesity-induced phenotype switch of murine and human ATMs. Thus, we show, for the first time, that the presence of ATMs is a general trait of mammals. The interaction between the adipose cells and SVF immune cells might be evolutionarily conserved among mammals.

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Section: Discussionsupporting

confidence: 67%

Adipose tissue macrophages in non-rodent mammals: a comparative study

et al. 2015

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“…We observed blocking PD-1 decreased parasite load and increased TNF-␣ concentration. Study showed that increased production of TNF-␣ with decreased intracelular survival of L. infantum in canine macrophages (Turchetti et al, 2015). Our findings suggesting that PD-1 blocking promotes TNF-␣ production and contribute to control of parasite multiplication.…”

Section: Discussionsupporting

confidence: 54%

“…The increase in TNF-␣ concentration observed after blocking PD-1 and its ligands may be related to increased microbicidal activity because the resistance of the intracellular survival of L. infantum in canine macrophages is mainly associated with the increased production of this cytokine (Turchetti et al, 2015). It was also reported that TNF-␣ enhances nitric oxide production in canine macrophages (Pinelli et al, 2000).…”

Section: Discussionmentioning

confidence: 97%

PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis

et al. 2016

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Dogs infected with Leishmania infantum have a reduced number of T lymphocytes. PD-1 (Programmed cell death 1) a new member of the B7-CD28 family that is expressed by immune cells, and its binding to PD-L1 (CD274) or PD-L2 (CD273) induces the deactivation or apoptosis of T cells. This study aimed to evaluate the expression of PD-1 and its ligands, as well as blocking in the induction of apoptosis in T lymphocytes, TNF-α, IL-4 and nitric oxide production by leucokocytes from PBMC and spleen and the parasite load in dogs with visceral leishmaniasis (VL). Our results showed that the expression of PD1 and its ligands was increased in CD3(+) T cells and CD21(+) B lymphocytes within the peripheral blood and splenic mononuclear cells of dogs with VL. In peripheral blood monocytes, only PD-1 ligands exhibited increased expression; however, in spleen macrophages, increased expression of both PD-1 and its ligands was observed. Levels of apoptosis in peripheral blood and splenic T lymphocytes were higher in dogs with VL compared to healthy dogs. Blocking monoclonal antibodies to PD-1 and its ligands in the culture of mononuclear cells from the peripheral blood and spleen decreased the amount of CD3(+) T lymphocyte apoptosis. The concentration of nitric oxide, TNF-α and IL-4 increased in the culture supernatants of peripheral blood mononuclear cells treated with a blocking monoclonal antibody against PD-1. The TNF-α concentration increased in the culture supernatants of splenic cells following all treatments with antibodies blocking PD-1 and its ligands; however, the amount of IL-4 increased only in the presence of a PD-1 blocking agent. Treatment with a PD-1 blocking monoclonal antibody in the mononuclear peripheral blood of dogs with VL reduced the parasite burden while increased TNF-α. We conclude that in canine visceral leishmaniasis, PD-1 and its ligands are involved in the induction of T lymphocyte apoptosis and in regulating the production of nitric oxide, TNF-α, and IL-4, as well as the parasitic load.

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“…gondii infection demonstrated an intrinsic defect of Nod2 KO T lymphocytes to produce IL-2 and differentiate into Th1 lymphocytes [14]. Based on an inverse correlation between Nod2 transcript levels and the intracellular survival of Leishmania infantum in macrophages [150], it has been proposed that Nod2 might also play a role in host defense against Leishmania . By contrast, Nod2 has virtually no impact on the outcome of the infections with T .…”

Section: Parasites and Yeastsmentioning

confidence: 99%

Nod2: The intestinal gate keeper

et al. 2017

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Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular pattern recognition receptor that senses bacterial peptidoglycan (PGN)-conserved motifs in cytosol and stimulates host immune response. The association of NOD2 mutations with a number of inflammatory pathologies, including Crohn disease (CD), Graft-versus-host disease (GVHD), and Blau syndrome, highlights its pivotal role in host–pathogen interactions and inflammatory response. Stimulation of NOD2 by its ligand (muramyl dipeptide) activates pro-inflammatory pathways such as nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), and Caspase-1. A loss of NOD2 function may result in a failure in the control of microbial infection, thereby initiating systemic responses and aberrant inflammation. Because the ligand of Nod2 is conserved in both gram-positive and gram-negative bacteria, NOD2 detects a wide variety of microorganisms. Furthermore, current literature evidences that NOD2 is also able to control viruses’ and parasites’ infections. In this review, we present and discuss recent developments about the role of NOD2 in shaping the gut commensal microbiota and pathogens, including bacteria, viruses, and parasites, and the mechanisms by which Nod2 mutations participate in disease occurrence.

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Transcription of innate immunity genes and cytokine secretion by canine macrophages resistant or susceptible to intracellular survival of Leishmania infantum

Cited by 37 publications

References 20 publications

Adipose tissue macrophages in non-rodent mammals: a comparative study

Adipose tissue macrophages in non-rodent mammals: a comparative study

PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis

Nod2: The intestinal gate keeper

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