Effects of IFN-γ, TNF-α, IL-10 and TGF-β on Neospora caninum infection in rat glial cells

Jesus, Erica Etelvina Viana de; Pinheiro, Alexandre Moraes; Santos, Alana Batista dos; Freire, Songelí Menezes; Tardy, M.; El-Bachá, Ramon dos Santos; Costa, Sílvia Lima; Costa, Maria de Fátima Dias

doi:10.1016/j.exppara.2012.11.016

Cited by 32 publications

(32 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Higher levels of IFN-γ and IL-12 are triggered in N. caninum- infected macrophages [28] and in N. caninum -infected mice [20], and they are critical cytokines for host resistance to N. caninum [29–32]. The production of TNF-α is also essential in controlling N. caninum infection [31, 33, 34]. In addition, similar to LPS, TNF-α is sufficient for NLRP3 inflammasome priming [35, 36].…”

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome activation in murine macrophages caused by Neospora caninum infection

et al. 2017

View full text Add to dashboard Cite

Background Neospora caninum is an intracellular parasite that causes significant economic losses in cattle industry. Understanding the host resistance mechanisms in the innate immune response to neosporosis could facilitate the exploration of approaches for controlling N. caninum infection. The NLR inflammasome is a multiprotein platform in the cell cytoplasm and plays critical roles in the host response against microbes.Methods Neospora caninum-infected wild-type (WT) macrophages and Nlrp3 −/− macrophages, and inhibitory approaches were used to investigate inflammasome activation and its role in N. caninum infection. Inflammasome RT Profiler PCR Arrays were used to identify the primary genes involved in N. caninum infection. The expression of the sensor protein NLRP3, processing of caspase-1, secretion of IL-1β and cell death were detected. Neospora caninum replication in macrophages was also assessed.ResultsMany NLR molecules participated in the recognition of N. caninum, especially the sensor protein NLRP3, and further study revealed that the NLRP3 distribution became punctate in the cell cytoplasm, which facilitated inflammasome activation. Inflammasome activation-mediated caspase-1 processing and IL-1β cleavage in response to N. caninum infection were observed and were correlated with the time of infection and number of infecting parasites. LDH-related cell death was also observed, and this death was regarded as beneficial for the clearance of N. caninum. Treatment of N. caninum-infected macrophages with caspase-1, pan-caspase and NLRP3 inhibitors led to the impaired release of active IL-1β and a failure to restrict parasite replication. And Neospora caninum infected peritoneal macrophages from Nlrp3-deficient mice displayed greatly decreased release of active IL-1β and the failure of caspase-1 cleavage.ConclusionsThe NLRP3 inflammasome can be activated in N. caninum-infected macrophages, and plays a protective role in the host response to control N. caninum.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-017-2197-2) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome activation in murine macrophages caused by Neospora caninum infection

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In association, WT (Dectin-1 + ) mice presented dendritic cells and macrophages with reduced IL-12p40 production after contact with live tachyzoites, which by its turn is followed by an increased parasite burden in both acute and chronic phases of infection. An effective control of infections by intracellular pathogens is closely linked to an innate immune response that culminates in the activation of an adaptive response, capable of neutralizing forms of the parasite disseminated through the blood stream and lymphatic system (57, 58). With that intent, antigen presentation assumes a central role in the activation of effective adaptive immune responses (59).…”

Section: Discussionmentioning

confidence: 99%

Dectin-1 Compromises Innate Responses and Host Resistance against Neospora caninum Infection

et al. 2017

View full text Add to dashboard Cite

Neospora caninum is an intracellular protozoan parasite that has drawn increasing interest due to its association with worldwide repetitive bovine abortions, which cause billionaire losses to the meat and dairy industries annually. Innate immunity plays an important role in infection control, and N. caninum activates the production of inflammatory mediators through toll-like receptors, NOD-like receptors, and mitogen-activated protein kinase signaling pathways. Advances in the knowledge of initial host–parasite interactions are desirable for the design of control measures against the infection, obliterating its pathogenesis. In that sense, we here aimed to describe the role of the innate C-type lectin receptor Dectin-1 during the infection by N. caninum. With that intent, we observed that the absence of Dectin-1, observed in genetically depleted (Dectin-1−/−) mice or competitively inhibited by an inert agonist [laminarin (LAM)], rescued 50% of the mice infected with lethal doses of N. caninum. Dectin-1−/− and LAM-treated mice also presented a reduction in the parasite load during acute and chronic phases, associated with decreased inflammatory scores in the central nervous system. Among all the cell phenotypes that migrated to the initial site of infection, dendritic cells and macrophages gained subpopulations with high Dectin-1 surface expression. The impairment of the receptor in these cells led to a decreased parasite burden, as well as augmented production of IL-12p40. We also found that Dectin-1+ cells produced less reactive oxygen species (ROS) at the initial site of the infection, while mice deficient in NADPH oxidase isoform 2 (NOX2−/−) were not able to control parasite replication and produce IL-12p40, even upon LAM treatment. Interestingly, the absence of functional Dectin-1 did not alter the susceptibility of mice against closely related Toxoplasma gondii. In conclusion, the gathered data suggest that Dectin-1 is involved in the parasite-induced downmodulation of ROS, and other key molecules triggered for the control of N. caninum infection and are a promising target for future development of protocols intended for intervention against neosporosis.

show abstract

“…TNF-α plays several therapeutic roles within the body, including immunostimulation, resistance to tumors, and sleep regulation2650. TNF-α is also an important mediator of resistance against infectious diseases225152535455. For example, in experimental leishmaniasis, insufficient TNF-α is associated with progressive disease and death53.…”

Section: Discussionmentioning

confidence: 99%

“…For example, in experimental leishmaniasis, insufficient TNF-α is associated with progressive disease and death53. In neosporiasis, exogenous TNF-α reduced Neospora caninum tachyzoites numbers in cultures in a dose-dependent manner54. In cerebral toxoplasmosis, TNF-α acts synergistically with IFN-γ, resulting in an antiparasitic mechanism in brain cells22.…”

Section: Discussionmentioning

confidence: 99%

Identification of a TNF-α inducer MIC3 originating from the microneme of non-cystogenic, virulent Toxoplasma gondii

Qiu

Wang

Zhang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Toxoplasma gondii is an opportunistic parasite with avirulent cystogenic and highly virulent non-cystogenic isolates. Although non-cystogenic strains are considered the most virulent, there are also marked genetic and virulence differences among these strains. Excretory-secretory antigens (ESAs) of T. gondii are critical for the invasion process and the immune response of the host. To better understand the differences in virulence between non-cystogenic T. gondii isolates, we studied ESAs of the RH strain (Type I), and the very prevalent in China, but less virulent TgCtwh3 strain (Chinese 1). ESAs of RH and TgCtwh3 triggered different levels of TNF-α production and macrophage M1 polarization. Using iTRAQ analysis, 27 differentially expressed proteins originating from secretory organelles and surface were quantified. Of these proteins, 11 microneme-associated proteins (MICs), 6 rhoptry proteins, 2 dense granule proteins and 5 surface proteins were more abundant in RH than in TgCtwh3. The protein-protein correlation network was employed to identify the important functional node protein MIC3, which was upregulated 5-fold in RH compared with TgCtwh3. MIC3 was experimentally confirmed to evoke a TNF-α secretory response, and it also induced macrophage M1 polarization. This result suggests that MIC3 is a potentially useful immunomodulator that induces TNF-α secretion and macrophage M1 polarization.

show abstract

Effects of IFN-γ, TNF-α, IL-10 and TGF-β on Neospora caninum infection in rat glial cells

Cited by 32 publications

References 40 publications

NLRP3 inflammasome activation in murine macrophages caused by Neospora caninum infection

NLRP3 inflammasome activation in murine macrophages caused by Neospora caninum infection

Dectin-1 Compromises Innate Responses and Host Resistance against Neospora caninum Infection

Identification of a TNF-α inducer MIC3 originating from the microneme of non-cystogenic, virulent Toxoplasma gondii

Contact Info

Product

Resources

About