Modeling of viral–bacterial coinfections at the molecular level using agonists of innate immunity receptors

Sviriaeva, Ekaterina; Korneev, Kirill V.; Drutskaya, Marina S.; Nedospasov, Sergei A.; Kuprash, Dmitry V.

doi:10.1134/s1607672916060053

Cited by 5 publications

(3 citation statements)

References 13 publications

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“…TLR11, along with TLR5, may also determine the outcome of Salmonella infection [19]. So, this inter‐TLR dependency may serve as the basis for co‐infection profile [28,29]. Finally, as TLRs are thus suggested to contribute to specific infection profile and as TLRs influence the adaptive immune response, it is possible that the nature of infection may be associated with the propensity of triggering a specific autoimmune disease [30].…”

Section: Discussionmentioning

confidence: 99%

Interdependencies between Toll‐like receptors in Leishmania infection

et al. 2021

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Multiple pathogen‐associated molecular patterns (PAMPs) on a pathogen's surface imply their simultaneous recognition by the host cell membrane‐located multiple PAMP‐specific Toll‐like receptors (TLRs). The TLRs on endosomes recognize internalized pathogen‐derived nucleic acids and trigger anti‐pathogen immune responses aimed at eliminating the intracellular pathogen. Whether the TLRs influence each other's expression and effector responses—termed TLR interdependency—remains unknown. Herein, we first probed the existence of TLR interdependencies and next determined how targeting TLR interdependencies might determine the outcome of Leishmania infection. We observed that TLRs selectively altered expression of their own and of other TLRs revealing novel TLR interdependencies. Leishmania major—an intra‐macrophage parasite inflicting the disease cutaneous leishmaniasis in 88 countries—altered this TLR interdependency unfolding a unique immune evasion mechanism. We targeted this TLR interdependency by selective silencing of rationally chosen TLRs and by stimulation with selective TLR ligands working out a novel phase‐specific treatment regimen. Targeting the TLR interdependency elicited a host‐protective anti‐leishmanial immune response and reduced parasite burden. To test whether this observation could be used as a scientific rationale for treating a potentially fatal L. donovani infection, which causes visceral leishmaniasis, we targeted the inter‐TLR dependency adopting the same treatment regimen. We observed reduced splenic Leishman–Donovan units accompanied by host‐protective immune response in susceptible BALB/c mice. The TLR interdependency optimizes TLR‐induced immune response by a novel immunoregulatory framework and scientifically rationalizes targeting TLRs in tandem and in sequence for redirecting immune responses against an intracellular pathogen.

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Section: Discussionmentioning

confidence: 99%

Interdependencies between Toll‐like receptors in Leishmania infection

et al. 2021

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“…Pneumonia-induced sepsis provides a clinically relevant model because airway infections often lead to secondary infection and subsequent acute respiratory distress syndrome, bacteremia, damage to the lungs, and multiple organ failure [20,96,97]. The model is relatively simple and reproducible and allows several alternative routes to administer bacteria, including intranasal (i.n.…”

Section: Intraperitoneal Injection Of a Fecal Solution Or Cecal Slurry (Cs)mentioning

confidence: 99%

“…These mice may have limited diversity of the microbiota, which directly affects the immune system and the development of pathological conditions [128]. Moreover, persistent virus infections (for example, herpesviruses) are activated in humans, but not in SPF mice, with septic complications and may change the resistance to bacterial coinfections [72,96,97]. "Dirty" mice are possibly better suitable for mimicking human pathologies [129].…”

Section: Experimental Models Of Sepsis: Limitations and Development Strategiesmentioning

confidence: 99%

Mouse Models of Sepsis and Septic Shock

Korneev

2019

Mol Biol

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An extensive network of regulation of systemic inflammation makes development of a reproducible experimental model of sepsis a complex task. There is no single mouse model that can capture all clinical aspects of this complicated pathology. However, a combination of existing approaches can go a long way towards analysis of specific mechanisms of sepsis development and to the design of novel therapeutic approaches. This review describes the popular mouse models of sepsis and septic shock, as well as their limitations and development strategies.

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Mechanisms of changes in immune response during bacterial coinfections of the respiratory tract

Sviriaeva

Korneev

Drutskaya

et al. 2016

Biochemistry Moscow

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Acute diseases of the respiratory tract are often caused by viral pathogens and accompanying secondary bacterial infections. It is known that the development of such bacterial complications is caused mainly by a decreased infiltration with immune system cells and by suppressed inflammation in the lungs. There are significant advances in understanding the mechanisms of secondary infections, although many details remain unclear. This review summarizes current knowledge of the molecular and cellular changes in the host organism that can influence the course of bacterial coinfections in the respiratory tract.

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Modeling of viral–bacterial coinfections at the molecular level using agonists of innate immunity receptors

Cited by 5 publications

References 13 publications

Interdependencies between Toll‐like receptors in Leishmania infection

Interdependencies between Toll‐like receptors in Leishmania infection

Mouse Models of Sepsis and Septic Shock

Mechanisms of changes in immune response during bacterial coinfections of the respiratory tract

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