Filarial thioredoxin reductase exerts anti-inflammatory effects upon lipopolysaccharide induced inflammation in macrophages

Joardar, Nikhilesh; Bhattacharya, Rajarshi; Halder, Satyajit; Sen, Animesh; Biswas, Swadesh Ranjan; Jana, Kuladip; Babu, Santi P. Sinha

doi:10.1016/j.ijbiomac.2021.10.200

Cited by 6 publications

(2 citation statements)

References 34 publications

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“…Antioxidants, such as glutathione S-transferases (GSTs), are detoxification enzymes that play an important role in protection against the free radicals generated by host immune cells, decreasing pro-inflammatory responses both in DCs and macrophages (106)(107)(108)(109)144).…”

Section: Helminth Secreted Proteinsmentioning

confidence: 99%

How to train your myeloid cells: a way forward for helminth vaccines?

Doolan,

Putananickal,

Tritten

et al. 2023

Front. Immunol.

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Soil-transmitted helminths affect approximately 1.5 billion people worldwide. However, as no vaccine is currently available for humans, the current strategy for elimination as a public health problem relies on preventive chemotherapy. Despite more than 20 years of intense research effort, the development of human helminth vaccines (HHVs) has not yet come to fruition. Current vaccine development focuses on peptide antigens that trigger strong humoral immunity, with the goal of generating neutralizing antibodies against key parasite molecules. Notably, this approach aims to reduce the pathology of infection, not worm burden, with only partial protection observed in laboratory models. In addition to the typical translational hurdles that vaccines struggle to overcome, HHVs face several challenges (1): helminth infections have been associated with poor vaccine responses in endemic countries, probably due to the strong immunomodulation caused by these parasites, and (2) the target population displays pre-existing type 2 immune responses to helminth products, increasing the likelihood of adverse events such as allergy or anaphylaxis. We argue that such traditional vaccines are unlikely to be successful on their own and that, based on laboratory models, mucosal and cellular-based vaccines could be a way to move forward in the fight against helminth infection. Here, we review the evidence for the role of innate immune cells, specifically the myeloid compartment, in controlling helminth infections. We explore how the parasite may reprogram myeloid cells to avoid killing, notably using excretory/secretory (ES) proteins and extracellular vesicles (EVs). Finally, learning from the field of tuberculosis, we will discuss how anti-helminth innate memory could be harnessed in a mucosal-trained immunity-based vaccine.

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Section: Helminth Secreted Proteinsmentioning

confidence: 99%

How to train your myeloid cells: a way forward for helminth vaccines?

Doolan,

Putananickal,

Tritten

et al. 2023

Front. Immunol.

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“…TLR4-dependent downstream signaling in DC subsets with differing cellular responses invites additional mechanistic research regarding the role of these glycans in immune response modulation. Setaria cervi thioredoxin reductase (TrxR) shows 100% sequence identity with B. malayi TrxR isoform C. In addition to its antioxidant activity, TrxR possesses anti-inflammatory activity in macrophages with inhibition of the TLR4/NF-κB axis, down-regulation of the inflammasome pathway, and activation of AAM [25] (Figure 1C).…”

Section: Filariae Regulate Prr Signalingmentioning

confidence: 99%

Harnessing Immune Evasion Strategy of Lymphatic Filariae: A Therapeutic Approach against Inflammatory and Infective Pathology

Bhoj

Togre

Khatri³

et al. 2022

Vaccines

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Human lymphatic filariae have evolved numerous immune evasion strategies to secure their long-term survival in a host. These strategies include regulation of pattern recognition receptors, mimicry with host glycans and immune molecules, manipulation of innate and adaptive immune cells, induction of apoptosis in effector immune cells, and neutralization of free radicals. This creates an anti-inflammatory and immunoregulatory milieu in the host: a modified Th2 immune response. Therefore, targeting filarial immunomodulators and manipulating the filariae-driven immune system against the filariae can be a potential therapeutic and prophylactic strategy. Filariae-derived immunosuppression can also be exploited to treat other inflammatory diseases and immunopathologic states of parasitic diseases, such as cerebral malaria, and to prevent leishmaniasis. This paper reviews immunomodulatory mechanisms acquired by these filariae for their own survival and their potential application in the development of novel therapeutic approaches against parasitic and inflammatory diseases. Insight into the intricate network of host immune-parasite interactions would aid in the development of effective immune-therapeutic options for both infectious and immune-pathological diseases.

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