CD4+ and CD19+ splenocytes undergo apoptosis during an experimental murine infection with Taenia crassiceps

López-Briones, Sergio; Sciutto, Edda; Ventura, Josep L.; Zentella, Alejandro; Fragoso, Gladis

doi:10.1007/s00436-003-0829-2

Cited by 12 publications

(5 citation statements)

References 43 publications

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“…In addition, during an ex vivo evaluation splenocytes of the experimental mice showed a high level of TGFβ and Foxp3 expression in comparison with control cells (Zepeda et al 2016). Similar in vitro results have been reported for apoptosis in CD4 + and CD19 + splenocytes of 30-day infected mice exposing to cysticercal antigens (Lopez-Briones et al 2003). Given the critical role of Th1 lymphocytes in protection against early establishment of this infection (Peón et al 2013), it seems that depletion of host CD4 + T cells through apoptosis is an intelligent strategy to set up and secure prolonged infection.…”

Section: Cestodessupporting

confidence: 85%

Helminth-induced apoptosis: a silent strategy for immunosuppression

Zakeri

2017

Parasitology

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During microbial infections, both innate and adaptive immunity are activated. Viruses and bacteria usually induce an acute inflammation in the first setting of infection, which helps the eliciting an effective immune response. In contrast, macroparasites such as helminths are a highly successful group of invaders known to be capable of maintaining a chronic infestation with the minimum instigation. Undoubtedly, generating such an immunoregulatory environment requires the exploitation of various immunosuppressive mechanisms to debilitate host immunity supporting their survival and replication. Several mechanisms have been recognized whereby helminths prolong their infections including an increase of immunoregulatory cells, inhibition of Th1 or Th2 responses, targeting pattern recognition receptors (PRRs) and lowering the immune cells quantity via induction of apoptosis. Apoptosis is a programmed intracellular process involving a series of consecutive downstream signalling event evolved to cell death. It plays a pivotal role in several immunological reactions in particular deletion of autoreactive immune cells. Helminth-triggered apoptosis in immune cells exhausts host immunity, which paves the way for generating a permissive environment and chronic infection. This review provides a compilation of recent investigations discussing the apoptotic mechanisms exploited by different worms and the immunological consequences of immune cell death. Finally, the anti-cancer effects of some worm-derived molecules due to their apoptotic effects are discussed, highlighting as potentially druggable candidates to combat cancer.

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Section: Cestodessupporting

confidence: 85%

Helminth-induced apoptosis: a silent strategy for immunosuppression

Zakeri

2017

Parasitology

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“…Similar immunosuppressive events occurred when supernatant from cultured H. diminuta was used, suggesting that secretory/excretory products from the worm, when afforded access to the host immune cells could reduce their activation in vivo -a supposition supported by the reduced Con A responsiveness of splenocytes from mice that received the H. diminuta extract intraperitoneally. Similar events have been observed with other cestodes and in the case of Taenia crassiceps and E. multilocularis, increased CD4 + T cell apoptosis and the production of a macrophage-derived factor were implicated as part of their immunosuppressive activity (Rakha et al 1991 ;Lopez-Briones et al 2003). However, analysis of apoptosis in Con A¡H.…”

Section: Discussionmentioning

confidence: 62%

“…Many examples can be cited to illustrate how parasites can affect the behaviour, physiology and immune responses of their hosts. In the case of parasitic helminths, all of the major groups of worms have been shown to either contain or secrete factors that are immunosuppressive, reducing proliferative responses, turning off or skewing cytokine responses, inducing apoptosis or modulating immune cell signal transduction events (Duvaux-Miret et al 1992 ;Persat et al 1996 ;Allen & MacDonald, 1998 ;Dematteis et al 2001 ;Satoguina et al 2002 ;van der Kleij et al 2002 ;Lopez-Briones et al 2003).…”

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confidence: 99%

Immune modulation by a high molecular weight fraction from the rat tapeworm Hymenolepis diminuta

Wang

McKay

2005

Parasitology

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The host-parasite relationship is exquisitely specific. In exploiting the host niche, a variety of helminth parasites have been shown to directly manipulate their hosts' immune responses. We assessed the ability of a whole-worm extract of Hymenolepis diminuta to modulate immune cell activation. Immune cells isolated from human blood or rodent spleens were activated with the T cell mitogen, concanavalin A (Con A) +/- H. diminuta extract and cytokine production (i.e. IL-2, -4, -10, -12) and proliferation assessed by ELISA and [3H]thymidine incorporation 24 and 72 h post-treatment, respectively. Co-treatment with the H. diminuta extract (100 microg protein/ml) virtually abolished Con A-induced immune cell proliferation, which was not due to increased apoptosis. Boiling of the worm extract reduced its anti-proliferative effect and fractionation indicated that a > 50 kDa component was predominantly responsible for the inhibition of Con A-induced immune cell proliferation. Cytokine determinations revealed that the H. diminuta extract significantly reduced Con A-stimulated IL-2 and IL-4, but enhanced the production of IFNy, IL-12 and IL-10. The increased IL-12 was due to an LPS contaminant in the extract and a helminth-derived 'IL-12'-like peptide that bound in the ELISA and Western blots. In contrast, a H. diminuta-derived factor directly stimulated IL-10 production by murine splenocytes, and contaminating LPS synergistically enhanced the production of IL-10. Thus, H. diminuta has the potential to block stimulated T cell proliferation and, by inhibiting IL-4 and promoting IL-10 production, may bias the immune environment towards one of immunoregulation and away from IL-4 dominated T helper 2 type events.

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“…Moreover, taken in account the data obtained using STAT6–/– mice is unlikely that NKT cells (early IL‐4 producers) have a possible role as the earlier cell responding to glycan structures of T. crassiceps antigens. Regarding whether or not apoptosis or cell cycle arrest is operating as the main mechanisms involved on the inhibition of T‐cell proliferation, more experiments are necessary; however, in experimental cysticercosis an increase in apoptotic CD4 + cells has been reported (39). On the other hand, the suppressive effect of macrophages recruited by Brugia was not associated to apoptosis because T cells in cocultures were still producing cytokines, indicating they were alive (40).…”

Section: Discussionmentioning

confidence: 99%

Intact glycans from cestode antigens are involved in innate activation of myeloid suppressor cells

Gómez-García

López-Marı́n²,

Saavedra³

et al. 2005

Parasite Immunology

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During helminthic infections, strong Th2 type-biased responses concomitant with impaired cell-proliferative responses to parasitic and unrelated antigens are major immunological hallmarks. Parasite glycan structures have been proposed to play a role in modulating these responses. To understand early events related to immune modulation during cestode infection, we have examined the role of intact glycans of antigens from Taenia crassiceps in the recruitment of innate cells. Soluble antigens from this cestode contained higher levels of carbohydrates than proteins. Intraperitoneal injection of the antigens rapidly recruited a cell population expressing F4/80(+)/Gr-1(+)surface markers, which adoptively suppressed naïve T-cell proliferation in vitro in response to anti-CD3/CD28 MAb stimulation in a cell-contact dependent manner. Soluble antigens with altered glycans by treatment with sodium periodate significantly reduced the recruitment of F4/80(+)/Gr1(+)cells, concomitantly their suppressive activity was abrogated, indicating that glycans have a role in the early activation of these suppressor cells. Using C3H/HeJ and STAT6-KO mice, we found that expansion and suppressive activity of F4/80(+)Gr1(+)cells induced by T. crassiceps intact antigens was TLR4 and Th2-type cytokine independent. Together with previous studies on nematode and trematode parasites, our data support the hypothesis that glycans can be involved on a similar pathway in the immunoregulation by helminths.

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CD4+ and CD19+ splenocytes undergo apoptosis during an experimental murine infection with Taenia crassiceps

Cited by 12 publications

References 43 publications

Helminth-induced apoptosis: a silent strategy for immunosuppression

Helminth-induced apoptosis: a silent strategy for immunosuppression

Immune modulation by a high molecular weight fraction from the rat tapeworm Hymenolepis diminuta

Intact glycans from cestode antigens are involved in innate activation of myeloid suppressor cells

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