TLR11 or TLR12 silencing reduces Leishmania major infection

Shukla, Divanshu; Chandel, Himanshu Singh; Srivastava, Sunit K.; Chauhan, Prashant; Pandey, Surya Prakash; Patidar, Ashok; Banerjee, Raja; Chattopadhyay, Debprasad; Saha, Bhaskar

doi:10.1016/j.cyto.2017.10.005

Cited by 15 publications

(11 citation statements)

References 14 publications

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“…In vitro studies (Table 1) were the first to propose and demonstrate that miltefosine induces a Th1 response via various immunological pathways. Applying miltefosine to Leishmania -infected splenocytes resulted in an induction of a Th1 response shown primarily by increased IFN-γ (19, 29–31). IFN-γ enables class switching from immunoglobulin G1 (IgG1) to IgG2.…”

Section: Resultsmentioning

confidence: 99%

Systematic Review of Host-Mediated Activity of Miltefosine in Leishmaniasis through Immunomodulation

Palić

Bhairosing

Beijnen

et al. 2019

Antimicrob Agents Chemother

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Host immune responses are pivotal for the successful treatment of the leishmaniases, a spectrum of infections caused by Leishmania parasites. Previous studies speculated that augmenting cytokines associated with a type 1 T-helper cell (Th1) response is necessary to combat severe forms of leishmaniasis, and it has been hypothesized that the antileishmanial drug miltefosine is capable of immunomodulation and induction of Th1 cytokines. A better understanding of the immunomodulatory effects of miltefosine is central to providing a rationale regarding synergistic mechanisms of activity to combine miltefosine optimally with other conventional and future antileishmanials that are currently under development. Therefore, a systematic literature search was performed to evaluate to what extent and how miltefosine influences the host Th1 response. Miltefosine’s effects observed in both a preclinical and a clinical context associated with immunomodulation in the treatment of leishmaniasis are evaluated in this review. A total of 27 studies were included in the analysis. Based on the current evidence, miltefosine is not only capable of inducing direct parasite killing but also of modulating the host immunity. Our findings suggest that miltefosine-induced activation of Th1 cytokines, particularly represented by increased gamma interferon (IFN-γ) and interleukin 12 (IL-12), is essential to prevail over the Leishmania-driven Th2 response. Differences in miltefosine-induced host-mediated effects between in vitro, ex vivo, animal model, and human studies are further discussed. All things considered, an effective treatment with miltefosine is acquired by enhanced functional Th1 cytokine responses and may further be enhanced in combination with immunostimulatory agents.

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Section: Resultsmentioning

confidence: 99%

Systematic Review of Host-Mediated Activity of Miltefosine in Leishmaniasis through Immunomodulation

Palić

Bhairosing

Beijnen

et al. 2019

Antimicrob Agents Chemother

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“…L donovani (MHOM/In83/Ag83) was maintained in RPMI‐1640 containing penicillin (100 U/mL), streptomycin (100 µg/mL), 2‐mercaptoethanol (50 µmol/L), sodium pyruvate (1 µmol/L), L‐Glutamine (2 mmol/L) and 10% FBS (GIBCO‐BRL). The parasite virulence was maintained by the passage of 2 × 10 7 (i.v) stationary‐phase L donovani promastigotes through BALB/c mice …”

Section: Methodsmentioning

confidence: 99%

“…Real‐time PCR was performed on Step One Plus Real‐Time PCR Systems (Applied Biosystems) under the following conditions: 95°C for 30 s, 45 cycles of 95°C for 5 s, 60°C for 34 s. Relative quantitation was done using the comparative threshold (ΔΔC t ) method. mRNA expression levels of the target genes were normalized against those of GAPDH and expressed as relative fold change compared with untreated controls …”

Section: Methodsmentioning

confidence: 99%

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LmjMAPK10 offers protection against Leishmania donovani infection

Kumar

Zutshi

Patidar

et al. 2020

Parasite Immunology

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Aims This study aimed at evaluating the DNA vaccination efficacy of Leishmania major‐derived MAPK10 against Leishmania donovani infection. Methods and Results MAPK10 is one of the 15 mitogen‐activated protein kinases (MAPKs) of Leishmania major. Herein, we expressed the gene through a mammalian vector and tested whether priming with this gene would offer protection against L donovani infection. We report that LmjMAPK10 DNA vaccination using a mammalian expression vector significantly reduces the parasite burden. The protection is accompanied by host‐protective T‐cell functions, TH1‐type cytokines and elevated leishmanial antigen‐specific IgG2a isotype response. T‐cell response to the L donovani/challenge infection is associated with increase in IL‐12 and IFN‐γ, but reduced IL‐10 and IL‐4 production. Conclusions LmjMAPK10 is cross‐protective against L donovani infection.

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“…Therefore, TLR9 appears to play a key role in infections by L. major or L. infantum [2]. On the other hand, TLR11 and TLR12 play an important role in an L. major infection, evidenced by the fact that the silencing of these receptors reduces the parasite burden, enhances the level of IFN-γ, and diminishes the production of IL-4 [68].…”

Section: Tlrs Contribute To the Effective Control Of Parasite Infectimentioning

confidence: 99%

TLR-Mediated Host Immune Response to Parasitic Infectious Diseases

Aguirre-Garcı́a¹,

Rojas-Bernabé²,

Gómez-García³

et al. 2020

Toll-Like Receptors

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Toll-like receptors (TLRs) are important for the host immune response to a variety of pathogens, including bacteria, viruses, fungi, and parasites. These receptors become activated upon recognizing pathogen-associated molecular patterns (PAMPs) and thus initiate the innate immune response to the corresponding pathogen. A key aspect of TLRs is their activation of signaling that leads to cytokine production and an inflammatory response. Additionally, TLRs act as the bridge between innate and acquired immunity, enhancing phagocytosis and the process of killing parasites. We herein focus on how parasites (protozoans and helminths) and their derived products have the capability of stimulating or evading the host response by triggering or inhibiting TLR activation. Parasites often develop successful survival strategies that imply interference with the host immune response. Accordingly, many of these organisms have molecules that modulate inflammation and other aspects of host immunity. Taking advantage of such mechanisms, there are some anti-inflammatory therapies based on human infection with helminths. Helminths and protozoans influence the activity of various TLRs, especially TLR2, TLR4, and TLR9. A better understanding of the role of TLRs and their parasite-derived ligands should certainly provide new therapeutic tools for combatting various parasitic and inflammatory diseases.

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TLR11 or TLR12 silencing reduces Leishmania major infection

Cited by 15 publications

References 14 publications

Systematic Review of Host-Mediated Activity of Miltefosine in Leishmaniasis through Immunomodulation

Systematic Review of Host-Mediated Activity of Miltefosine in Leishmaniasis through Immunomodulation

LmjMAPK10 offers protection against Leishmania donovani infection

TLR-Mediated Host Immune Response to Parasitic Infectious Diseases

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