IDO, COX and iNOS have an important role in the proliferation of Neospora caninum in neuron/glia co-cultures

Jesus, Lívia Bacelar de; Santos, Alana Batista dos; Jesus, Erica Etelvina Viana de; Santos, Rosalina Guedes Donato; Grangeiro, Maria Socorro; Bispo-da-Silva, A.; Arruda, Maiara Reis; Argolo, Deivison Silva; Pinheiro, Alexandre Moraes; Bachá, R.S. El; Costa, Sílvia Lima; Costa, M.F.D.

doi:10.1016/j.vetpar.2019.01.003

Cited by 7 publications

(9 citation statements)

References 56 publications

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“…Several enzymes involved in tryptophan degradation were upregulated in MØs infected with both isolates except IDO1, which was upregulated only in MØ1H. Because restriction of N. caninum proliferation induced by IDO1 activity has been demonstrated in vitro [67], this antiparasitic mechanism of the host cell may be related to the lower proliferation of Nc-Spain1H in bovine MØs [14].…”

Section: Discussionmentioning

confidence: 92%

Neospora caninum infection induces an isolate virulence-dependent pro-inflammatory gene expression profile in bovine monocyte-derived macrophages

et al. 2020

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Background: Neospora caninum is an obligate intracellular parasite, and its ability to survive inside host immune cells may be a key mechanism for the establishment of infection in cattle. In vitro studies carried out by our group have shown that N. caninum is able to replicate in bovine macrophages (MØs), alter their microbicidal mechanisms and exploit their motility. Furthermore, host-cell control seems to be isolate virulence-dependent. Methods: To investigate the molecular basis underlying the innate responses in MØs against N. caninum and the mechanisms of parasite manipulation of the host cell environment, the transcriptome profile of bovine monocytederived MØs infected with high-virulence (Nc-Spain7) or low-virulence (Nc-Spain1H) N. caninum isolates was studied. Results: Functional enrichment revealed upregulation of genes involved in chemokine signalling, inflammation, cell survival, and inhibition of genes related with metabolism and phagolysosome formation. MØs activation was characterized by the induction of a predominantly M1 phenotype with expression of TLR2, TLR3 and TLR9 and activation of the NF-ƙB signalling pathway. Heat-killed N. caninum tachyzoites failed to activate NF-ƙB, and to inhibit lysosomal activity and apoptosis, which indicates active modulation by the parasite. The FoxO signalling pathway, Th1-Th2 differentiation, glycosaminoglycan degradation and apoptosis were pathways enriched only for low virulent Nc-Spain1H infection. In addition, Nc-Spain1H infection upregulated the IL12A and IL8 pro-inflammatory cytokines, whereas IL23 was downregulated by high virulent Nc-Spain7. Conclusions: This study revealed mechanisms implicated in the recognition of N. caninum by bovine MØs and in the development of the subsequent immune response. NF-ƙB seems to be the main signalling pathway implicated in the pro-inflammatory bovine MØs response against this pathogen. Apoptosis and phagolysosome maturation are processes repressed by N. caninum infection, which may guarantee its intracellular survival. The results also indicate that Nc-Spain7 may be able to partially circumvent the pro-inflammatory response whereas Nc-Spain1H induces a protective response to infection, which may explain the more efficient transmission of the high-virulence Nc-Spain7 isolate observed in vivo.

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Section: Discussionmentioning

confidence: 92%

Neospora caninum infection induces an isolate virulence-dependent pro-inflammatory gene expression profile in bovine monocyte-derived macrophages

et al. 2020

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“…Recently, Jesus et al 16 demonstrated that the infection of glial cells by N. caninum also activated Trp catabolism and that could be an antiparasitic mechanism. The results herein described showed that infection of glial cell cultures by N. caninum , besides astrogliosis, also increased the expression of mRNA KMO.…”

Section: Discussionmentioning

confidence: 99%

“… 11 - 14 On the other hand, the infection of glial-neuron co-cultures with N. caninum tachyzoites after modulated by IFN-γ showed preservation of neurite outgrowth and induced the activation of indolamine 2, 3 dioxygenase (IDO), the first and rate-limiting enzyme of tryptophan catabolism through the KP, controlling the parasite proliferation. 15 , 16 …”

Section: Introductionmentioning

confidence: 99%

Activation of the Kynurenine Pathway and Production of Inflammatory Cytokines by Astrocytes and Microglia Infected With Neospora caninum

Argolo

Borges

Freitas

et al. 2022

Int J�Tryptophan�Res

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In the central nervous system, astrocytes and microglia contribute to homeostasis, regulating the immune response to infectious agents. Neospora caninum is an obligate intracellular protozoan that infects different animal species and it is encysted in their nervous tissue while triggering an immune response modulated by glia. This study aimed to evaluate the infection of primary cultures of rat glial cells by N. caninum through the catabolites of tryptophan, the expression of inflammatory mediators and the integrity of neural tissue. Infection with this coccidium resulted in morphological and functional changes, particularly astrogliosis and microgliosis, and increased the expression of the inflammatory mediators TNF, IL1β, IL-10, and arginase, as well as mRNA for CCL5 and CCL2, molecules involved in the CNS chemotaxis. The infection with N. caninum in glial cells also triggered the activation of the tryptophan pathway, characterized by increased kynurenine 2,3 monooxygenase (KMO) mRNA expression, and by the production of the excitotoxin quinolinic acid (QUIN). Moreover, glia-neuron co-cultures, when exposed to the secretome derived from N. caninum infected glial cells, presented greater neurons distribution and formation of neurite extensions, associated to morphological changes in astrocytes compatible with neuro-preservation. Considering that the tryptophan catabolism is associated to immune response, these findings suggest that glial activation in N. caninum infection should be responsible for modulating the inflammatory status in an attempt to restore the nervous system homeostasis, since excessive inflammatory response can cause irreversible damage to tissue preservation.

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“…This effect was noticed in cases of bovine neutrophils [131], caprine monocytes [133], and canine neutrophils [134]. Indoleamine 2,3-Dioxygenase (IDO) is reported to participate in the control of N. caninum infection through tryptophan degradation-dependent pathways and mediated by IFN-γ [186,188,[195][196][197].…”

Section: Dendritic Cells and Macrophagesmentioning

confidence: 97%

From Signaling Pathways to Distinct Immune Responses: Key Factors for Establishing or Combating Neospora caninum Infection in Different Susceptible Hosts

Fereig

Nishikawa

2020

Pathogens

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Neospora caninum is an intracellular protozoan parasite affecting numerous animal species. It induces significant economic losses because of abortion and neonatal abnormalities in cattle. In case of infection, the parasite secretes numerous arsenals to establish a successful infection in the host cell. In the same context but for a different purpose, the host resorts to different strategies to eliminate the invading parasite. During this battle, numerous key factors from both parasite and host sides are produced and interact for the maintaining and vanishing of the infection, respectively. Although several reviews have highlighted the role of different compartments of the immune system against N. caninum infection, each one of them has mostly targeted specific points related to the immune component and animal host. Thus, in the current review, we will focus on effector molecules derived from the host cell or the parasite using a comprehensive survey method from previous reports. According to our knowledge, this is the first review that highlights and discusses immune response at the host cell–parasite molecular interface against N. caninum infection in different susceptible hosts.

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IDO, COX and iNOS have an important role in the proliferation of Neospora caninum in neuron/glia co-cultures

Cited by 7 publications

References 56 publications

Neospora caninum infection induces an isolate virulence-dependent pro-inflammatory gene expression profile in bovine monocyte-derived macrophages

Neospora caninum infection induces an isolate virulence-dependent pro-inflammatory gene expression profile in bovine monocyte-derived macrophages

Activation of the Kynurenine Pathway and Production of Inflammatory Cytokines by Astrocytes and Microglia Infected With Neospora caninum

From Signaling Pathways to Distinct Immune Responses: Key Factors for Establishing or Combating Neospora caninum Infection in Different Susceptible Hosts

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