Cytokine-dependent and–independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling

Costales, Jaime A.; Daily, Johanna P.; Burleigh, Barbara A.

doi:10.1186/1471-2164-10-252

Cited by 53 publications

(70 citation statements)

References 53 publications

(54 reference statements)

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“…Transcriptomic studies have demonstrated that Trypanosoma cruzi infection triggers a prominent type I IFN response in a variety of primary cell types in vitro and at the site of intradermal inoculation of mice (10,13). The goal of the present study was to determine whether type I IFN-dependent signaling plays a role in innate host protection against T. cruzi.…”

Section: Discussionmentioning

confidence: 99%

“…T. cruzi triggers a type I interferon response in a variety of primary cell types in vitro and in vivo in a parasite strain-dependent manner (10,13). The role of type I IFNs in experimental T. cruzi infection is presently unclear given inconsistent outcomes observed in type I IFN receptor knockout (IFNAR Ϫ/Ϫ ) mice (12,22,51).…”

Section: Ifnarmentioning

confidence: 99%

“…Despite observations that T. cruzi elicits a prominent type I IFN response early in infection (10,13,52), it is presently unclear if type I IFNs play a role in innate resistance to T. cruzi (12,22,51). The goal of the present study was to determine whether type I IFN-dependent signaling plays a role in innate host resistance to T. cruzi infection.…”

mentioning

confidence: 96%

“…Transcriptomic studies reveal changes in expression of a large number of IFN-inducible genes in a variety of primary mammalian cell types infected with T. cruzi in vitro and at the site of inoculation in vivo (10,13,52).…”

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confidence: 99%

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Type I Interferons Increase Host Susceptibility to Trypanosoma cruzi Infection

et al. 2011

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Trypanosoma cruzi, the protozoan parasite that causes human Chagas' disease, induces a type I interferon (IFN) (IFN-␣/␤) response during acute experimental infection in mice and in isolated primary cell types. To examine the potential impact of the type I IFN response in shaping outcomes in experimental T. cruzi infection, groups of wild-type (WT) and type I IFN receptor-deficient (IFNAR ؊/؊ ) 129sv/ev mice were infected with two different T. cruzi strains under lethal and sublethal conditions and several parameters were measured during the acute stage of infection. The results demonstrate that type I IFNs are not required for early host protection against T. cruzi. In contrast, under conditions of lethal T. cruzi challenge, WT mice succumbed to infection whereas IFNAR ؊/؊ mice were ultimately able to control parasite growth and survive. T. cruzi clearance in and survival of IFNAR ؊/؊ mice were accompanied by higher levels of IFN-␥ production by isolated splenocytes in response to parasite antigen. The suppression of IFN-␥ in splenocytes from WT mice was independent of IL-10 levels. While the impact of type I IFNs on the production of IFN-␥ and other cytokines/chemokines remains to be fully determined in the context of T. cruzi infection, our data suggest that, under conditions of high parasite burden, type I IFNs negatively impact IFN-␥ production, initiating a detrimental cycle that contributes to the ultimate failure to control infection. These findings are consistent with a growing theme in the microbial pathogenesis field in which type I IFNs can be detrimental to the host in a variety of nonviral pathogen infection models.

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Section: Discussionmentioning

confidence: 99%

Section: Ifnarmentioning

confidence: 99%

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confidence: 96%

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confidence: 99%

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Type I Interferons Increase Host Susceptibility to Trypanosoma cruzi Infection

et al. 2011

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“…Analysis of high-dose infections with T. cruzi reveals upregulation of IFN-I and interferon-stimulated genes as the most prominent host cell response to infection (2)(3)(4)24). If one excludes these cytokine-dependent responses, the host cell response to infection appears to be quite variable but with the common feature of changes in stress response genes and genes controlling cell growth (4).…”

Section: Discussionmentioning

confidence: 99%

Generation ofTrypanosoma cruzi-Specific CD8⁺T-Cell Immunity Is Unaffected by the Absence of Type I Interferon Signaling

Martin

Tarleton

2010

Infect Immun

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Trypanosoma cruzi is a protozoan parasite that causes human Chagas' disease, a leading source of congestive heart failure in Central and South America. CD8 ؉ T cells are critical for control of T. cruzi infection, and CD8 ؉ T cells recognizing the immunodominant trans-sialidase gene-encoded peptide TSKB20 (ANYKFTLV) account for approximately 30% of the total CD8 ؉ T-cell population at the peak of infection in C57BL/6 mice. Type I interferons (IFN-I) are pleiotropic cytokines that play a critical role in both innate and adaptive immunity against a variety of infections, but their induction and their role in infection are dictated by the infectious agent. Because type I IFNs and IFN-responsive genes are evident early after T. cruzi infection of host cells, we examined the influence of IFN-I on the development of CD8 ؉ T-cell responses during this infection. Mice lacking the receptor for IFN-I (IFNARKO) and their wild-type counterparts both developed chronic infections and generated similar frequencies of immunodominant TSKB20-and subdominant TSKB18-specific CD8 ؉ T cells following T. cruzi infection. In contrast, peak TSKB20-specific CD8 ؉ T-cell responses generated during infection with vaccinia virus engineered to express TSKB20 were approximately 2.5-fold lower in IFNARKO mice than B6 mice, although after viral clearance, the frequencies of TSKB20-specific CD8 ؉ T cells stabilized at similar levels. Together, these data suggest that IFN-I induction and biology are dependent upon the microbial context and emphasize the need to investigate various infection models for a full understanding of CD8 ؉ T-cell development. CD8ϩ T cells are an essential contributor to the control of the intracellular protozoan pathogen Trypanosoma cruzi, the causative agent of human Chagas' disease. T. cruzi trypomastigotes can infect virtually any nucleated cell, and once in the host cell cytoplasm, transform into and replicate as amastigotes. The cytoplasmic localization of T. cruzi allows for parasite-derived proteins to be available for processing and presentation through the major histocompatibility complex class I (MHC-I) pathway, and obliteration of this pathway leads to early death for T. cruzi-infected mice (21,22). T. cruzi-infected mice depleted of CD8 ϩ T cells also succumb to infection during the acute phase (within 35 days after infection) (20). The annotated genome of T. cruzi contains more than 12,000 genes (5), yet despite this genetic complexity and the resultant enormous number of potential epitopes, the CD8 ϩ T-cell response to T. cruzi is focused on only a few peptides. In B6 mice infected with the Brazil strain of T. cruzi, CD8 ϩ T cells recognizing TSKB20 (ANYKFTLV) and TSKB18 (ANYDFTLV) expand significantly and represent over 40% of the total CD8 ϩ

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Role of ROS in T. cruzi Intracellular Development

Andrade

Dias

2019

Oxidative Stress in Microbial Diseases

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Cytokine-dependent and–independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling

Cited by 53 publications

References 53 publications

Type I Interferons Increase Host Susceptibility to Trypanosoma cruzi Infection

Type I Interferons Increase Host Susceptibility to Trypanosoma cruzi Infection

Generation ofTrypanosoma cruzi-Specific CD8⁺T-Cell Immunity Is Unaffected by the Absence of Type I Interferon Signaling

Role of ROS in T. cruzi Intracellular Development

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Cytokine-dependent and–independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling

Cited by 53 publications

References 53 publications

Type I Interferons Increase Host Susceptibility to Trypanosoma cruzi Infection

Type I Interferons Increase Host Susceptibility to Trypanosoma cruzi Infection

Generation ofTrypanosoma cruzi-Specific CD8+T-Cell Immunity Is Unaffected by the Absence of Type I Interferon Signaling

Role of ROS in T. cruzi Intracellular Development

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Generation ofTrypanosoma cruzi-Specific CD8⁺T-Cell Immunity Is Unaffected by the Absence of Type I Interferon Signaling