Expression of inducible nitric oxide synthase in macrophages inversely correlates with parasitism of lymphoid tissues in dogs with visceral leishmaniasis

Abstract

BackgroundThere are only a few studies reporting the role of nitric oxide metabolites for controlling macrophage intracellular parasitism, and these are controversial. Therefore, the present study aimed to evaluate the expression of inducible nitric oxide synthase (iNOS) in the lymph nodes and spleen of dogs affected by visceral leishmaniasis through immunohistochemistry and to determine its correlation with tissue parasite burden and serum interferon (IFN)-γ levels. Twenty-eight dogs were selected and assigned to one of two groups, symptomatic (n = 18) and asymptomatic (n = 10), according to clinical status and laboratory evaluation. A negative control group (n = 6) from a non-endemic region for visceral leishmaniasis was included as well.ResultsParasite density (amastigotes/mm2) was similar between clinical groups in the lymph nodes (P = 0.2401) and spleen (P = 0.8869). The density of iNOS+ cells was higher in infected dogs compared to controls (P < 0.05), without a significant difference in lymph node (P = 0.3257) and spleen (P = 0.5940) densities between symptomatic and asymptomatic dogs. A positive correlation was found between the number of iNOS+ cells in lymph nodes and interferon-γ levels (r = 0.3776; P = 0.0303), and there was a negative correlation between parasites and iNOS+ cell densities both in lymph nodes (r = −0.5341; P = 0.0034) and spleen (r = −0.4669; P = 0.0329).ConclusionThe negative correlation observed between tissue parasitism and the expression of iNOS may be a reflection of NO acting on the control of parasites.

Cellular apoptosis and nitric oxide production in PBMC and spleen from dogs with visceral leishmaniasis

“…The high frequency of cells producing NO observed in the spleen of dogs with leishmaniasis confirmed previous results in which higher proportions of cells producing iNOS were observed in dogs with leishmaniasis [26,8] Conversely, the levels of NO were reduced in the spleen, suggesting that the leishmanicidal function is impaired, in fact symptomatic dogs showed lower iNOS mRNA expression than asymptomatic [27]. and high iNOS expression was observed in macrophages containing little or no amastigotes internalized in the liver samples, skin and lymph node of dogs with VL.…”

“…The use of an intracellular probe for detecting NO allowed for its quantification, while previous studies used iNOS for the detection of NO in dogs infected with VL in order to demonstrate the production of NO [26,10,25]. However, the detection of iNOS positive cells does not define NO levels, leading to inconclusive results.…”

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

“…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. However, whereas mouse M1 macrophages are high NO producers, conflicting results have been obtained regarding whether canine macrophages have a NO burst when they fight pathogens (Sanches et al 2014). Our data also suggest that NO synthesis is associated with a subpopulation of canine ATMs in obesity.…”

Heterogeneity of macrophages in canine histiocytic ulcerative colitis

“…71 In addition, iNOS-deficient mice are more susceptible to intestinal damage induced by acetic acid and show a longer course of colitis. 72 Activated canine macrophages have been demonstrated to produce large amounts of NO for the effective destruction of several pathogens, such as canine leishmaniasis [73][74][75] or Trypanosoma cruzi infection. 76 However, studies investigating iNOS in the canine gut and in canine HUC are not available so far.…”