High iNOS expression in macrophages in canine leishmaniasis is associated with low intracellular parasite burden

Zafra, R.; Jaber, José Raduán; Pérez-Écija, Alejandro; Barragán, Agustín; Martı́nez-Moreno, A.; Pérez, J.

doi:10.1016/j.vetimm.2008.02.022

Cited by 48 publications

(48 citation statements)

References 18 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of macrophages in canine histiocytic ulcerative colitis

Nolte¹,

Junginger²,

Baum

et al. 2017

Innate Immun

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Histiocytic ulcerative colitis (HUC) is a chronic enteropathy which most notably occurs in Boxer dogs and French bulldogs. The inflamed mucosa is hallmarked by large, foamy, periodic acid-Schiff (PAS)-positive macrophages infiltrating the colonic mucosa. As little is known about their origin and phenotype, an immunohistochemical study was performed using different macrophage markers. Generally, canine colonic macrophages showed high expression of ionised calciumbinding adaptor molecule 1 and MHC class II. In canine HUC, macrophages revealed up-regulation of lysozyme and L1 Ag but decreased CD163 expression compared with controls, suggesting them to be pro-inflammatory cells, whereas the healthy colonic mucosa was characterised by an anti-inflammatory macrophage phenotype. In addition, PAS reaction was used to discriminate macrophage subpopulations. PAS -macrophages displayed higher expression of L1 Ag and CD64, whereas PAS þ cells, which were only present in HUC patients, were characterised by increased expression of lysozyme, inducible nitric oxide synthase and CD204. This indicates PAS þ cells to be mature macrophages contributing to the inflammatory process, which are most likely maintained by differentiation of immature PAS -macrophages continuously recruited from blood monocytes. In summary, macrophage heterogeneity in canine HUC probably illustrates their different maturation states and functions compared with the healthy animals.

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Section: Discussionmentioning

confidence: 99%

Heterogeneity of macrophages in canine histiocytic ulcerative colitis

Nolte¹,

Junginger²,

Baum

et al. 2017

Innate Immun

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“…Likewise, it is known that, in addition to deficient production of lytic enzymes (iNOS) in macrophages infected with Leishmania (L.) chagasi (Zafra et al 2008), inhibition of the ability to express molecules of MHC class II in the cell membrane of phagocytes also occurs. Similarly, this expression may appear internalized in the cell membrane of amastigotes, as previously described in L. amazonensis (Leão et al 1995), affecting both the function of parasite lysis and the antigen presentation to CD4+ T lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Immune response pattern of the popliteal lymph nodes of dogs with visceral leishmaniasis

et al. 2010

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The present study aimed to estimate the cell response and parasite load in the popliteal lymph nodes of dogs with visceral leishmaniasis (VL), comparing these findings with the clinical staging of the disease. From the necropsy, 33 dogs were classified as symptomatic (S), asymptomatic (A), or oligosymptomatic (O). Cytology and histopathology were used to determine any presence of microscopic lesions and immunohistochemistry, for parasite load. Dog hyperimmune serum was used as the primary antibody. The inflammatory infiltrate in lymph nodes consisted of macrophages and plasmocytes. The granulomas invaded the trabecular and sinusoid regions and sometimes compressed the lymphocytes of the cortical region (atrophy) and medullary cord cells. Parasite load intensity was unrelated to the density of the macrophages infiltrating the lymph node. Significant differences in parasite load (P < 0.05) were observed between the three groups of infected dogs. Follicular hyperplasia of the cortical region occurred among A and O, while follicular atrophy predominated among S. The parasite load was the greatest among S, followed by O. It can be concluded that, regardless of clinical condition, the most evident cell response consisted of macrophages and plasmocytes. Lymphoid atrophy was observed among animals with intense granulomatous reaction and high parasite load, such as among the symptomatic dogs (P < 0.05). Likewise, the oligosymptomatic dogs also presented high density of parasites in the lymph nodes. Thus, we can confirm that dogs with clinical manifestations of VL have an immune system that is less effective for controlling infection by Leishmania chagasi, thereby favoring parasite multiplication.

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“…Mechanisms of parasite survival and persistence in the host have been thoroughly investigated, and include suppression of iNOS and the parasite entry into iNOS negative cells [49]. The iNOS expression by macrophages plays an important role during the control of leishmania infection in dogs [52], thisNO may be involved in the long-term protection of dogs against natural Leishmania infection and in the clinical presentation of canine leishmaniasis [53]. Application of potential prodrugs to cultures of infected mouse macrophages that were deficient in iNOS caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity [54].…”

Section: Leishmania Spmentioning

confidence: 99%

Involvement of nitric oxide and its up/down stream molecules in the immunity against parasitic infections

Nahrevanian

2009

Braz J Infect Dis

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Nitric oxide (NO) is a potent mediator with diverse roles in regulating cellular functions and signaling pathways. The NO synthase (NOS) enzyme family consists of three major isoforms, which convey variety of messages between cells, including signals for vasorelaxation, neurotransmission and cytotoxicity. This family of enzymes are generally classified as neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Increased levels of NO are induced from iNOS during infection; while eNOS and nNOS may be produced at the baseline in normal conditions. An association of some key cytokines appears to be essential for NOS gene regulation in the immunity of infections. Accumulating evidence indicates that parasitic diseases are commonly associated with elevated production of NO. NO plays a role in the immunoregulation and it is implicated in the host non-specific defence in a variety of infections. Nevertheless, the functional role of NO and NOS isoforms in the immune responses of host against the majority of parasites is still highly controversial. In the present review, the role of parasitic infections will be discussed in the controversy related to the NO production and iNOS gene expression in different parasites and a variety of experimental models.

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High iNOS expression in macrophages in canine leishmaniasis is associated with low intracellular parasite burden

Cited by 48 publications

References 18 publications

Heterogeneity of macrophages in canine histiocytic ulcerative colitis

Heterogeneity of macrophages in canine histiocytic ulcerative colitis

Immune response pattern of the popliteal lymph nodes of dogs with visceral leishmaniasis

Involvement of nitric oxide and its up/down stream molecules in the immunity against parasitic infections

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