CD40 Signaling in Macrophages Induces Activity against an Intracellular Pathogen Independently of Gamma Interferon and Reactive Nitrogen Intermediates

Andrade, Rosa; Portillo, Jose‐Andres C.; Wessendarp, Matthew; Subauste, Carlos S.

doi:10.1128/iai.73.5.3115-3123.2005

Cited by 57 publications

(79 citation statements)

References 47 publications

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“…Furthermore Scheidegger et al (2005) showed that TNF-a treatment resulted in increased parasite proliferation in cultures of infected rat brain slices although the mechanisms remain obscure [46]. Recent reports have highlighted the existence of IFN-g independent means of T. gondii killing [47,48]. For example CD40-CD40L signalling appears to be sufficient for in vitro and in vivo killing of T. gondii independently of IFN-g or reactive nitrogen species [47,48].…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports have highlighted the existence of IFN-g independent means of T. gondii killing [47,48]. For example CD40-CD40L signalling appears to be sufficient for in vitro and in vivo killing of T. gondii independently of IFN-g or reactive nitrogen species [47,48]. Importantly, CD40/ CD40L signalling is critical for protection against TE with CD40L À/À mice demonstrating increased parasite proliferation [49].…”

Section: Discussionmentioning

confidence: 99%

“…Of significance these workers had previously demonstrated that IFN-g and TNF-a were insufficient to control the growth of T. gondii in neurones [45]. Furthermore Scheidegger et al (2005) showed that TNF-a treatment resulted in increased parasite proliferation in cultures of infected rat brain slices although the [47,48]. For example CD40-CD40L signalling appears to be sufficient for in vitro and in vivo killing of T. gondii independently of IFN-g or reactive nitrogen species [47,48].…”

Section: (C-f) Magnification Of the Area Depicted By The Box In (A) mentioning

confidence: 99%

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IL‐33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii

et al. 2010

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T1/ST2 is an immunoregulatory protein of the IL-1 receptor family that has recently been reported as being a component of the IL-33 receptor. IL-33 is a newly described cytokine known to amplify the Th2 response and reduce production of Th1 cytokines. The function of T1/ST2 during Toxoplasma gondii infection is as yet undescribed. Given the requirement of a balanced type 1/type 2 response for effective control of parasite number and immunopathology, it is likely that T1/ST2 may play a part in aiding this process. Accordingly, we have shown that T1/ST2 mRNA transcripts are upregulated in the brains of mice infected with T. gondii and that mice deficient in T1/ST2 demonstrated increased susceptibility to infection with T. gondii that correlated with increased pathology and greater parasite burden in the brains. Real-time PCR analysis of cerebral cytokine levels revealed increased mRNA levels of iNOS, IFN-c and TNF-a in infected T1/ST2 À/À mice. These effects were independent of changes in IL-10 production. This study provides the first evidence of a specific role for IL-33 receptor signalling in the brain as well as highlighting the requirement of this mechanism in limiting infection with an intracellular parasite.Key words: Encephalitis . IL-33 . IL-33 receptor . Th1/Th2 . Toxoplasma IntroductionThe receptor T1/ST2 is a member of the IL-1 receptor family that also includes the TLR and the IL-18R [1]. Further characterisation revealed that differential splicing of T1/ST2 mRNA led to production of two different transcripts encoding either a transmembrane form (ST2L) or a soluble, secreted form (sST2) [2]. T1/ST2 is expressed by a number of haematopoetic cells such as T cells, mast cells, macrophages, NK cells and invariant NKT cells [3][4][5][6][7]. ST2L has previously been used as a marker for Th2 cells although T1/ST2-negative Th2 cells exist with reports that ST2L may be better described as a marker of effector Th2 cells enhancing the Th2 response rather than aiding its development [3,[8][9][10]. As well as promoting a Th2 response ST2L has been shown to sequester the signalling molecules MyD88 and Mal to inhibit subsequent cytokine production following TLR ligation [10]. sST2 also plays a role in downregulating the inflammatory response [6,11]. 426T1/ST2 is the ligand-binding component of the receptor for the cytokine IL-33 which, together with the IL-1 receptor accessory protein, forms the IL-33 receptor [12,13]. IL-33 is a member of the IL-1 family with the ability to downregulate IFN-g production by Th1 cells in vitro and upregulate the production of the Th2 cytokines IL-5 and IL-13 from Th2 cells both in vitro and in vivo [12]. Therefore, the function of IL-33 reinforces the previously described role of T1/ST2 in enhancing a Th2 response while reducing a Th1 response.Protective immunity to the protozoan parasite Toxoplasma gondii relies on a delicate balance of type 1/type 2 immune responses to effectively control parasite proliferation and prevent pathology caused by an over-exuberant type-1 response [14]...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: (C-f) Magnification Of the Area Depicted By The Box In (A) mentioning

confidence: 99%

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IL‐33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii

et al. 2010

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“…Therefore, CD154 + T. gondii-reactive activated CD4 + T cells likely trigger CD40 signaling in macrophages and resident microglia. CD40 stimulation of macrophages allows them to acquire toxoplasmacidal activity (Andrade et al 2003(Andrade et al , 2005a(Andrade et al , b, 2006. This effect is not only mediated by recombinant CD154 or an agonistic anti-CD40 mAb but also by CD154 expressed on the membrane of activated CD4 + T cells (Andrade et al 2005a).…”

Section: Cd40 Transforms the Parasitophorous Vacuole Into A Compartmementioning

confidence: 99%

“…CD40 stimulation of macrophages allows them to acquire toxoplasmacidal activity (Andrade et al 2003(Andrade et al , 2005a(Andrade et al , b, 2006. This effect is not only mediated by recombinant CD154 or an agonistic anti-CD40 mAb but also by CD154 expressed on the membrane of activated CD4 + T cells (Andrade et al 2005a). Killing of T. gondii tachyzoites induced by CD40 does not require IFN-γ, or effector molecules downstream of this cytokine: NOS2 and Immune Related GTPases (IRG) (Andrade et al 2003, 2005a.…”

Section: Cd40 Transforms the Parasitophorous Vacuole Into A Compartmementioning

confidence: 99%

CD40, autophagy and Toxoplasma gondii

Subauste

2009

Mem. Inst. Oswaldo Cruz

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Autophagy as an innate immunity response against pathogens: a Tango dance

Aguilera,

Delgui,

Reggiori

et al. 2023

FEBS Letters

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Intracellular infections as well as changes in the cell nutritional environment are main events that trigger cellular stress responses. One crucial cell response to stress conditions is autophagy. During the last 30 years, several scenarios involving autophagy induction or inhibition over the course of an intracellular invasion by pathogens have been uncovered. In this review, we will present how this knowledge was gained by studying different microorganisms. We intend to discuss how the cell, via autophagy, tries to repel these attacks with the objective of destroying the intruder, but also how some pathogens have developed strategies to subvert this. These two fates can be compared with a Tango, a dance originated in Buenos Aires, Argentina, in which the partner dancers are in close connection. One of them is the leader, embracing and involving the partner, but the follower may respond escaping from the leader. This joint dance is indeed highly synchronized and controlled, perfectly reflecting the interaction between autophagy and microorganism.

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CD40 Signaling in Macrophages Induces Activity against an Intracellular Pathogen Independently of Gamma Interferon and Reactive Nitrogen Intermediates

Abstract: Gamma interferon (IFN-␥

Cited by 57 publications

References 47 publications

IL‐33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii

IL‐33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii

CD40, autophagy and Toxoplasma gondii

Autophagy as an innate immunity response against pathogens: a Tango dance

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