Role of nitric oxide in host defense against an extracellular, metazoan parasite, Brugia malayi

The direct effect of nitric oxide (NO) on the viability of Toxocara canis larvae was studied. We observed that the nitric oxide donors, SIN-1 and SNOG, exert no cytotoxic effect on the in vitro viability of T. canis larvae. In addition, we developed a model in rats to elucidate the role of NO during T. canis infection. We evaluated different indicators in four experimental groups: morphological parameters, the total number cells and cell types recovered, nitrite and protein concentration, lactate dehydrogenase and alkaline phosphatase enzymatic activity in the bronchoalveolar lavage fluid, lung index and detection of anti-T. canis specific antibodies. We observed significant differences between non-infected and infected groups. The infected animals treated with the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine were less damaged than infected, non-treated animals. Our results suggest that the in vivo inhibition of the synthesis of NO triggered by iNOS diminishes the deleterious effects of the parasite upon the host, especially the vascular alterations in the lungs. We could show that in vivo production of NO induced by infection with T. canis results in direct host damage. Thus, this induction may constitute an evasion/adaptation mechanism of the parasite.

Section: Discussionmentioning

confidence: 99%

In vivo inhibition of inducible nitric oxide synthase decreases lung injury induced by Toxocara canis in experimentally infected rats

Espinoza

Pérez-Arellano

Carranza

et al. 2002

“…However, NO-mediated effects on parasitaemia are reported much less frequently. The enhanced survival of B. malayi infective larvae after inhibition of NO synthesis (Rajan et al 1996) is outstanding in this context, because larval development takes place outside the blood. Other studies on extracellular, blood-dwelling parasite species did not ®nd antiparasitic effects of NO in vivo despite of well-documented susceptibility in vitro; for example, in schistosomes (Coulson et al 1998) and trypanosomes (Kaushik et al 1999).…”

Section: Discussionmentioning

confidence: 99%

“…In-vitro studies have demonstrated the susceptibility of ®larial parasites to NO attack , Thomas et al 1997. In the Brugia malayi model, the genetic knockout of the gene for iNOS, as well as pharmaceutical inhibition of NO synthesis, enhanced the survival rate of infective larvae (L3, Rajan et al 1996). Unfortunately, the development of B. malayi L3 in mice is abrogated before they reach maturity.…”

Section: Introductionmentioning

confidence: 99%

The role of nitric oxide in the innate resistance to microfilariae of Litomosoides sigmodontis in mice

Pfaff

Schulz‐Key

Soboslay

et al. 2000

Nitric oxide (NO) has been shown to be an important effector mechanism in the defence against various pathogens, including filariae. The production of NO, as well as H2O2, is induced by the Th1 cytokine IFN-gamma. Therefore, the microfilariae (mf) of filarial nematodes, which are known to elicit the release of IFN-gamma, may be a target of NO release. In this study, we found that mf of the filarial species Litomosoides sigmodontis were resistant to the attack of H2O2, but vulnerable to NO exposure in vitro by a chemical NO donor, as well as activated macrophages. Adult worms were considerably less affected by exposure to NO. In-vivo production of NO following injection of mf, in this and previous studies, suggested a central role in the defence to filariae. However, neither pharmaceutical inhibition of nitric oxide synthesis, nor genetic knockout of the gene for inducible nitric oxide synthase (iNOS), abrogated resistance to circulating mf in mice. Interestingly, however, iNOS-KO mice showed higher interleukin (IL)-2 responses and lower IL-10 production, compared to their wild-type counterparts. In conclusion, despite its effectiveness in vitro and the observed production of NO by ex vivo cells following infection, nitric oxide seems not to be an important factor in elimination of mf of L. sigmodontis in vivo. However, it may have a regulatory role in the immune response.

“…Oxidants that have been associated with nematode resistance include phagocytic oxidase (PHOX) (7), dual oxidase (DUOX) (6) and inducible nitric oxide synthase (NOS2A) (8). It is thought that reactive oxygen and nitrogen species (RONS) generated by these factors directly interact with the invading nematodes resulting in damage or lethality (9).…”

Section: Introductionmentioning

confidence: 99%

Nematode challenge induces differential expression of oxidant, antioxidant and mucous genes down the longitudinal axis of the sheep gut

Menzies

Reverter

Andronicos

et al. 2010

To characterize the role of a range of oxidant, antioxidant and mucous-related genes in the primary response to gastrointestinal nematodes, groups of genetically resistant sheep were challenged with either Haemonchus contortus or Trichostrongylus colubriformis and necropsied for retrieval of tissue at days 0, 3, 7, 14 and 21. To determine if the response was localized to the site of parasite infection, four different gut tissues were sampled: the abomasum, proximal and distal jejunum and ileum. Basal expression patterns of all candidate genes were determined using the day 0 (pre-challenge) samples. A conserved innate response involving elevated expression of dual oxidase, glutathione peroxidase and trefoil factor was initiated within 3 days of challenge and extended out to 21 days. An increase in host gene expression levels at the preferred site of infection (the abomasum for H. contortus and the proximal jejunum for T. colubriformis) was also common to both nematodes. However, these increases were concomitant with reduced expression in other areas of the gut suggesting a compartmentalized response. Other aspects of the response were parasite-specific, with T. colubriformis challenge inducing expression peaks at times corresponding to nematode life-stage transitions.