Helminth-induced apoptosis: a silent strategy for immunosuppression

Abstract

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.

Modulation of human dendritic cell activity by Giardia and helminth antigens

“…Moreover, apoptosis in DCs is a well‐established mechanism of immune‐evasion by P. falciparum and has also been reported for L. donovani . Whilst apoptosis has also been observed in DCs exposed to helminths, our current results suggest a marked difference in DC responses to either intestinal protozoan or helminth parasites. This may in part explain the lack of combined effects on cytokine secretion, for if Giardia induces either partial or total apoptosis before the helminth antigens are able to exert modulatory activity, then the overriding effect on the DC population may be that induced by Giardia .…”

Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles

“…Of note, this mutual relationship between worm and host evolves to reciprocal beneficial outcomes, as deworming can result in the emergence of immune-related disorders along with clinical manifestations ( 3 ). Various mechanisms have been identified by which helminths restrain host immune responses including expansion of regulatory cells ( 4 ), induction of apoptosis in immune cells ( 5 ), manipulation of pattern recognition receptors (PRRs) and downstream signaling ( 6 ), and suppression of Th1/Th2 cells and associated cytokines ( 7 ). However, there are likely to still be complex and unknown aspects of the strategies underpinning this sophisticated interface which are yet to be investigated ( 8 ).…”

Parasites as negative regulators of cancer

“…However, it can be attenuated in tumors with a higher degree of transformation and resistance to therapies [ 2 ]. Protozoa and helminths have been described as inducers of apoptosis, which is a survival mechanism, in cells of the immune system and epithelial cells [ 34 , 35 ]. This proapoptotic effect has also been tested in both in vivo and in vitro cancer models.…”