Review on the Role of Host Immune Response in Protection and Immunopathogenesis during Cutaneous Leishmaniasis Infection

Cutaneous leishmaniasis (CL) is a major public health problem worldwide and spreads to human via the bite of sand flies during blood meal. Following its inoculation, the promastigotes are immediately taken up by phagocytic cells and these leishmania-infected host cells produce proinflammatory cytokines that activate other immune cells and these infected host cells produce more cytokines and reactive nitrogen and oxygen species for efficient control of leishmania infection. Many experimental studies showed that resistance to infection with leishmania paraites is associated with the production of proinflammatory cytokines and activation of CD4+ Th1 response. On the other hand, vulnerability to this parasitic infection is correlated to production of T helper 2 cytokines that facilitate persistence of parasites and disease progression. In addition, some studies have also indicated that CD8+ T cells play a vital role in immune defense through cytokine production and their cytotoxic activity and excessive production of proinflammatory mediators promote amplified recruitment of cells. This could be correlated with excessive inflammatory reaction and ultimately resulted in tissue destruction and development of immunopathogenesis. Thus, there are contradictions regarding the role of immune responses in protection and immunopathogenesis of CL disease. Therefore, the aim of this paper was to review the role of host immune response in protection and its contribution to disease severity for CL infection. In order to obtain more meaningful data regarding the nature of immune response to leishmania, further in-depth studies focused on immune modulation should be conducted to develop better therapeutic strategies.

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Extracellular Vesicles in Viral Spread and Antiviral Response

Viruses ◽

10.3390/v12060623 ◽

2020 ◽

Vol 12 (6) ◽

pp. 623 ◽

Cited By ~ 5

Author(s):

Raquel Bello-Morales ◽

Inés Ripa ◽

José Antonio López-Guerrero

Keyword(s):

Immune Response ◽

Extracellular Vesicles ◽

Current Knowledge ◽

Host Immune Response ◽

Host Cells ◽

Viral Spread ◽

Viral Responses ◽

Hsv 1

Viral spread by both enveloped and non-enveloped viruses may be mediated by extracellular vesicles (EVs), including microvesicles (MVs) and exosomes. These secreted vesicles have been demonstrated to be an efficient mechanism that viruses can use to enter host cells, enhance spread or evade the host immune response. However, the complex interplay between viruses and EVs gives rise to antagonistic biological tasks—to benefit the viruses, enhancing infection and interfering with the immune system or to benefit the host, by mediating anti-viral responses. Exosomes from cells infected with herpes simplex type 1 (HSV-1) may transport viral and host transcripts, proteins and innate immune components. This virus may also use MVs to expand its tropism and evade the host immune response. This review aims to describe the current knowledge about EVs and their participation in viral infection, with a specific focus on the role of exosomes and MVs in herpesvirus infections, particularly that of HSV-1.

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The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response

Infection and Immunity ◽

10.1128/iai.00531-16 ◽

2016 ◽

Vol 84 (12) ◽

pp. 3458-3470 ◽

Cited By ~ 11

Author(s):

Mike Khan ◽

Jerome S. Harms ◽

Fernanda M. Marim ◽

Leah Armon ◽

Cherisse L. Hall ◽

...

Keyword(s):

Immune Response ◽

Second Messenger ◽

Host Immune Response ◽

Vital Role ◽

Host Cells ◽

Content Type ◽

Type Iv

Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host- Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a Δ bpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the Δ bpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase Δ cgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, Δ bpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection.

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Bacterial Cyclic Dinucleotides and the cGAS–cGAMP–STING Pathway: A Role in Periodontitis?

Pathogens ◽

10.3390/pathogens10060675 ◽

2021 ◽

Vol 10 (6) ◽

pp. 675

Author(s):

Samira Elmanfi ◽

Mustafa Yilmaz ◽

Wilson W. S. Ong ◽

Kofi S. Yeboah ◽

Herman O. Sintim ◽

...

Keyword(s):

Immune Response ◽

Periodontal Disease ◽

Innate Immune ◽

Host Cells ◽

Type I Interferons ◽

Type I ◽

Vaccine Adjuvants ◽

Cyclic Dinucleotides ◽

Sting Pathway

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms “STING”, “TBK 1”, “IRF3”, and “cGAS”—alone, or together with “periodontitis”. Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology.

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Mycobacterium tuberculosis adhesins: potential biomarkers as anti-tuberculosis therapeutic and diagnostic targets

Microbiology ◽

10.1099/mic.0.082206-0 ◽

2014 ◽

Vol 160 (9) ◽

pp. 1821-1831 ◽

Cited By ~ 22

Author(s):

Viveshree S. Govender ◽

Saiyur Ramsugit ◽

Manormoney Pillay

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Control Strategies ◽

Host Cells ◽

Tuberculosis Control ◽

Surface Molecules ◽

Host Pathogen Interaction ◽

Bacterial Aggregation ◽

Insight Into

Adhesion to host cells is a precursor to host colonization and evasion of the host immune response. Conversely, it triggers the induction of the immune response, a process vital to the host’s defence against infection. Adhesins are microbial cell surface molecules or structures that mediate the attachment of the microbe to host cells and thus the host–pathogen interaction. They also play a crucial role in bacterial aggregation and biofilm formation. In this review, we discuss the role of adhesins in the pathogenesis of the aetiological agent of tuberculosis, Mycobacterium tuberculosis. We also provide insight into the structure and characteristics of some of the characterized and putative M. tuberculosis adhesins. Finally, we examine the potential of adhesins as targets for the development of tuberculosis control strategies.

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Role of costimulatory molecules in immune response of patients with cutaneous leishmaniasis

Microbes and Infection ◽

10.1016/j.micinf.2004.09.015 ◽

2005 ◽

Vol 7 (1) ◽

pp. 86-92 ◽

Cited By ~ 6

Author(s):

Cecilia Favali ◽

Dirceu Costa ◽

Lilian Afonso ◽

Viviane Conceição ◽

Andréa Rosato ◽

...

Keyword(s):

Immune Response ◽

Cutaneous Leishmaniasis ◽

Costimulatory Molecules

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The possible role of the frontal and sub-parietal gland systems of the pentastomidReighardia sternae(Diesing, 1864) in the evasion of the host immune response

Parasitology ◽

10.1017/s0031182000048587 ◽

1979 ◽

Vol 78 (1) ◽

pp. 53-66 ◽

Cited By ~ 19

Author(s):

J. Riley ◽

J. L. James ◽

A. A. Banaja

Keyword(s):

Immune Response ◽

Alternative Explanation ◽

Surface Membrane ◽

Membrane System ◽

Host Immune Response ◽

Entire Surface ◽

Strong Immune Response ◽

Concomitant Immunity ◽

Host Parasite

SUMMARYThe frontal and sub-parietal glands of the pentastomidReighardia sternaeelaborate lamellate secretion which is poured on to the cuticle. The entire surface of the cuticle, including the mouth, hook pits and reproductive apertures, is coated with secretion. Electron microscope studies indicate that the glands are continuously active, which implies a turnover of surface membranes. The postulated function of these membranes is to protect certain vital areas of the host–parasite interface, notably the pores of ion-transporting cells, from the host immune response. The available evidence suggests that pentastomids do evoke a strong immune response but since most are long-lived they must circumvent it. We believe the surface membrane system to be instrumental in this. Studies on another pentastomid,Porocephalus crotaliin rats have shown that an immune response stimulated by a primary infection will kill subsequent infections and that the surface membranes are strongly immunogenic. Obvious parallels between this situation and that of schistosome infections in mammals are discussed. An alternative explanation of concomitant immunity is proposed.

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Immunity and its role in periodontal diseases

Romanian Journal of Stomatology ◽

10.37897/rjs.2017.1.4 ◽

2017 ◽

Vol 63 (1) ◽

pp. 24-27

Author(s):

Irina Dumitrache ◽

Keyword(s):

Immune Response ◽

Chronic Disease ◽

Periodontal Disease ◽

Clinical Efficacy ◽

Periodontal Diseases ◽

Adult Population ◽

Host Immune Response ◽

Immunomodulatory Therapy ◽

Common Chronic Disease

Periodontal disease is one of the most common chronic disease, with a prevalence between 5% and 30% in adult population aged 25-75. In the pathogenesis of periodontal disease, the host immune response has a great importance and in the last years it has been underlined the role of immunomodulatory therapy in the management of periodontal disease. Septilin is a herbal immunomodulatory with clinical efficacy proven in the periodontal disease.

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Leishmania donovani Secretory Mevalonate Kinase Regulates Host Immune Response and Facilitates Phagocytosis

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.641985 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tanvir Bamra ◽

Taj Shafi ◽

Sushmita Das ◽

Manjay Kumar ◽

Manas Ranjan Dikhit ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Leishmania Donovani ◽

Indian Subcontinent ◽

Parasite Burden ◽

Host Immune Response ◽

Host Cells ◽

Interleukin 4 ◽

Host Immune System ◽

Mevalonate Kinase

Summary StatementLeishmania secretes over 151 proteins during in vitro cultivation. Cellular functions of one such novel protein: mevalonate kinase is discussed here; signifying its importance in Leishmania infection.Visceral Leishmaniasis is a persistent infection, caused by Leishmania donovani in Indian subcontinent. This persistence is partly due to phagocytosis and evasion of host immune response. The underlying mechanism involves secretory proteins of Leishmania parasite; however, related studies are meagre. We have identified a novel secretory Leishmania donovani glycoprotein, Mevalonate kinase (MVK), and shown its importance in parasite internalization and immuno-modulation. In our studies, MVK was found to be secreted maximum after 1 h temperature stress at 37°C. Its secretion was increased by 6.5-fold in phagolysosome-like condition (pH ~5.5, 37°C) than at pH ~7.4 and 25°C. Treatment with MVK modulated host immune system by inducing interleukin-10 and interleukin-4 secretion, suppressing host’s ability to kill the parasite. Peripheral blood mononuclear cell (PBMC)-derived macrophages infected with mevalonate kinase-overexpressing parasites showed an increase in intracellular parasite burden in comparison to infection with vector control parasites. Mechanism behind the increase in phagocytosis and immunosuppression was found to be phosphorylation of mitogen-activated protein (MAP) kinase pathway protein, Extracellular signal-regulated kinases-1/2, and actin scaffold protein, cortactin. Thus, we conclude that Leishmania donovani Mevalonate kinase aids in parasite engulfment and subvert the immune system by interfering with signal transduction pathways in host cells, which causes suppression of the protective response and facilitates their persistence in the host. Our work elucidates the involvement of Leishmania in the process of phagocytosis which is thought to be dependent largely on macrophages and contributes towards better understanding of host pathogen interactions.

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The complex, bidirectional role of extracellular vesicles in infection

Biochemical Society Transactions ◽

10.1042/bst20200788 ◽

2021 ◽

Author(s):

Joni Renee White ◽

Priscila Dauros-Singorenko ◽

Jiwon Hong ◽

Frédérique Vanholsbeeck ◽

Anthony Phillips ◽

...

Keyword(s):

Immune Response ◽

Extracellular Vesicles ◽

Bacterial Pathogens ◽

Host Cells ◽

Signalling Molecules ◽

Host Pathogen ◽

Domains Of Life

Cells from all domains of life release extracellular vesicles (EVs), packages that carry a cargo of molecules that participate in communication, co-ordination of population behaviours, virulence and immune response mechanisms. Mammalian EVs play an increasingly recognised role to fight infection, yet may also be commandeered to disseminate pathogens and enhance infection. EVs released by bacterial pathogens may deliver toxins to host cells, signalling molecules and new DNA to other bacteria, and act as decoys, protecting infecting bacteria from immune killing. In this review, we explore the role of EVs in infection from the perspective of both the pathogen and host, and highlight their importance in the host/pathogen relationship. We highlight proposed strategies for EVs in therapeutics, and call attention to areas where existing knowledge and evidence is lacking.

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