Sialidase of Glaesserella parasuis augments inflammatory response via desialylation and abrogation of negative regulation of Siglec-5

Siglecs are sialic acid-binding immunoglobulin-like lectins that play an important role in tissue homeostasis, immune response, and pathogen infection. Bacterial sialidases act on natural ligands of Siglecs, interfering with the Siglec-mediated immune response. Glaesserella parasuis is a porcine bacterial pathogen that secretes sialidase. However, little is known about the sialidase of G. parasuis and its impact on immune regulation. Here, we used wild-type G. parasuis, a sialidase-deficient mutant, and complimentary strains to investigate the role of sialidase in porcine alveolar macrophage infection. Sialidase induced the release of proinflammatory cytokines, such as interleukin (IL)-1α, IL-6, and tumor necrosis factor alpha, from porcine alveolar macrophages. Moreover, sialidase desialylated the surface of porcine alveolar macrophages and altered the expression of Siglecs (the expression of Siglec-5 was reduced). Furthermore, sialidase led to a reduction in endogenous SH2 domain-containing protein tyrosine phosphatase (SHP-2) recruitment to Siglec-5 and simultaneously activated the inflammatory response via the mitogen-activated protein kinase and nuclear factor kappa light chain enhancer of activated B cell signaling pathways. This desialylation occurred before the release of proinflammatory cytokines, suggesting that the sialidase-induced inflammatory response was followed by reduced recruitment of SHP-2 to Siglec-5. Thus, this study is the first to demonstrate the role of sialidase in the inflammatory response of G. parasuis. This role resulted from the abrogation of negative regulation of Siglec-5 on proinflammatory cytokine release. This study helps to understand the molecular mechanism underlying the inflammatory response induced by sialidase secreted by G. parasuis and the acute inflammation caused by G. parasuis.

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PPARs in Alveolar Macrophage Biology

PPAR Research ◽

10.1155/2007/23812 ◽

2007 ◽

Vol 2007 ◽

pp. 1-12 ◽

Cited By ~ 9

Author(s):

Monica R. Smith ◽

Theodore J. Standiford ◽

Raju C. Reddy

Keyword(s):

Immune Response ◽

Inflammatory Response ◽

Alveolar Macrophage ◽

Alveolar Macrophages ◽

Crucial Role ◽

Respiratory Function ◽

Lung Diseases ◽

First Line ◽

Phagocytotic Activity

PPARs, most notably PPAR-γ, play a crucial role in regulating the activation of alveolar macrophages, which in turn occupy a pivotal place in the immune response to pathogens and particulates drawn in with inspired air. In this review, we describe the dual role of the alveolar macrophage as both a first-line defender through its phagocytotic activity and a regulator of the immune response. Depending on its state of activation, the alveolar macrophage may either enhance or suppress different aspects of immune function in the lung. We then review the role of PPAR-γand its ligands in deactivating alveolar macrophages—thus limiting the inflammatory response that, if unchecked, could threaten the essential respiratory function of the alveolus—while upregulating the cell's phagocytotic activity. Finally, we examine the role that inadequate or inappropriate PPAR-γresponses play in specific lung diseases.

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Giardia duodenalis extracellular vesicles regulate the proinflammatory immune response in mouse macrophages in vitro via the MAPK, AKT and NF-κB pathways

Parasites & Vectors ◽

10.1186/s13071-021-04865-5 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Panpan Zhao ◽

Lili Cao ◽

Xiaocen Wang ◽

Jianhua Li ◽

Jingquan Dong ◽

...

Keyword(s):

Immune Response ◽

Inflammatory Response ◽

Signaling Pathways ◽

Innate Immune Response ◽

Proinflammatory Cytokines ◽

Giardia Duodenalis ◽

Innate Immune ◽

Tnf Α ◽

Mouse Macrophages

Abstract Background Giardia duodenalis is an extracellular protozoan parasite that causes giardiasis in mammals. The presentation of giardiasis ranges from asymptomatic to severe diarrhea, and the World Health Organization lists it in the Neglected Diseases Initiative. Extracellular vesicles (EVs) are a key mediator of intracellular communication. Although previous studies have shown that G. intestinalis can regulate a host’s innate immune response, the role of G. intestinalis EVs (GEVs) in triggering a G. intestinalis-induced innate immune response remains to be further explored. Methods In this study, GEVs, G. intestinalis and GEVs + G. intestinalis were inoculated into macrophages, respectively. The transcription and secretion levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNF-α), were measured using real-time quantitative PCR (qPCR) and enzyme-linked immunosorbent assays (ELISAs). The phosphorylation levels of the MAPK, AKT and NF-κB signaling pathways in GEV-stimulated mouse macrophages were examined using western blotting and immunofluorescence methods. The roles of activated pathways in the GEV-triggered inflammatory response were determined using inhibition assays, western blotting and ELISAs. Results The results showed that pretreatment with GEVs enhanced with G. intestinalis (GEVs + G. intestinalis) induced IL-1β, IL-6 and TNF-α transcription and secretion from mouse macrophages compared to stimulation with either GEVs or G. intestinalis alone. Inoculation of mouse macrophages with GEVs upregulated the phosphorylation levels of the p38 MAPK, p44/42 MAPK (Erk1/2), AKT and NF-κB signaling pathways and led to the nuclear translocation of NF-κB p65. Blocking the activated p38, Erk and NF-κB signaling pathways significantly downregulated the secretion of proinflammatory cytokines, and blocking the activated AKT signaling pathway demonstrated reverse effects. Conclusions The results of this study reveal that GEVs can enhance G. intestinalis-induced inflammatory response levels in mouse macrophages through activation of the p38, ERK and NF-κB signaling pathways. The role of GEVs in regulating host cell immune responses may provide insights into exploring the underlying mechanisms in G. intestinalis–host interactions. Graphical abstract

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Inflammasomes inMycobacterium tuberculosis-Driven Immunity

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2017/2309478 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Sebastian Wawrocki ◽

Magdalena Druszczynska

Keyword(s):

Mycobacterium Tuberculosis ◽

Inflammatory Response ◽

Immune Responses ◽

Proinflammatory Cytokines ◽

Immune Cells ◽

Protein Complexes ◽

Inflammasome Activation ◽

Host Immune Responses ◽

Multimeric Protein

The development of effective innate and subsequent adaptive host immune responses is highly dependent on the production of proinflammatory cytokines that increase the activity of immune cells. The key role in this process is played by inflammasomes, multimeric protein complexes serving as a platform for caspase-1, an enzyme responsible for proteolytic cleavage of IL-1βand IL-18 precursors. Inflammasome activation, which triggers the multifaceted activity of these two proinflammatory cytokines, is a prerequisite for developing an efficient inflammatory response against pathogenicMycobacterium tuberculosis(M.tb). This review focuses on the role of NLRP3 and AIM2 inflammasomes inM.tb-driven immunity.

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RESPIRATORY SYNCYTIAL VIRUS LUNG INFECTION IN INFANTS: IMMUNOREGULATORY ROLE OF INFECTED ALVEOLAR MACROPHAGES

PEDIATRICS ◽

10.1542/peds.96.2.391 ◽

1995 ◽

Vol 96 (2) ◽

pp. 391-391

Author(s):

Leon S. Greos

Keyword(s):

Immune Response ◽

Respiratory Syncytial Virus ◽

Lung Injury ◽

Alveolar Macrophages ◽

Lung Infection ◽

Local Immune Response ◽

Rsv Infection ◽

Syncytial Virus

Alveolar macrophages are infected by RSV in vivo and coexpress potent immunomodulatory molecules that potentially regulate local immune response or lung injury caused by RSV infection.

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Acute Inflammatory Response to Sheep Red Blood Cells in Mice Treated with 2,3,7,8-Tetrachlorodibenzo-p-dioxin: The Role of Proinflammatory Cytokines, IL-1 and TNF

Toxicology and Applied Pharmacology ◽

10.1006/taap.1994.1169 ◽

1994 ◽

Vol 127 (2) ◽

pp. 331-335 ◽

Cited By ~ 27

Author(s):

A.B. Moos ◽

L. Baechersteppan ◽

N.I. Kerkvliet

Keyword(s):

Inflammatory Response ◽

Red Blood Cells ◽

Proinflammatory Cytokines ◽

Blood Cells ◽

Acute Inflammatory Response ◽

Sheep Red Blood Cells ◽

Tetrachlorodibenzo P Dioxin

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CD209 (DC-SIGN) – role in the work of the innate immunity and pathogen penetration

Veterinariya, Zootekhniya i Biotekhnologiya ◽

10.36871/vet.zoo.bio.202009007 ◽

2020 ◽

Vol 1 (9) ◽

pp. 64-71

Author(s):

E. A. Klimov ◽

◽

E. K. Novitskaya ◽

S. N. Koval’chuk ◽

◽

...

Keyword(s):

Immune Response ◽

Innate Immunity ◽

Dendritic Cells ◽

Inflammatory Response ◽

Signaling Pathway ◽

Adhesion Molecule ◽

Immune Evasion ◽

Intercellular Adhesion Molecule ◽

Lectin Receptor

Intercellular adhesion molecule CD209 (DC-SIGN) is a membrane C-type lectin receptor expressed on the surface of dendritic cells and macrophages. CD209 plays an important role in innate immunity. Many studies have shown the possibility of interaction of the CD209 molecule with a number of dangerous pathogens of humans and animals. This review summarizes information on the structure of the CD209 gene and its product, describes the role of the CD209 protein in the immune response, in the migration of dendritic cells from the blood to the tissue, and their interaction with neutrophils. The currently known signaling pathway of activation through the CD209 inflammatory response is presented. The role of CD209 as an endocytic antigen receptor and the participation of the protein in immune evasion of pathogens are discussed. The mechanisms known to date for the development of infections caused by pathogens of various nature in animals are described.

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

Journal of Immunology Research ◽

10.1155/2020/2496713 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Teshager Dubie ◽

Yasin Mohammed

Keyword(s):

Immune Response ◽

Cutaneous Leishmaniasis ◽

Proinflammatory Cytokines ◽

Parasitic Infection ◽

Host Immune Response ◽

Immune Defense ◽

Host Cells ◽

Infected Host ◽

Major Public Health Problem

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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CD4 T Cells Mediate Both Positive and Negative Regulation of the Immune Response to HIV Infection: Complex Role of T Follicular Helper Cells and Regulatory T Cells in Pathogenesis

Frontiers in Immunology ◽

10.3389/fimmu.2014.00681 ◽

2015 ◽

Vol 5 ◽

Cited By ~ 10

Author(s):

Chansavath Phetsouphanh ◽

Yin Xu ◽

John Zaunders

Keyword(s):

Immune Response ◽

T Cells ◽

Regulatory T Cells ◽

Hiv Infection ◽

Cd4 T Cells ◽

Negative Regulation ◽

T Follicular Helper Cells ◽

Helper Cells ◽

Follicular Helper

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The Role of the Immune Response in the Pathogenesis of Bronchiectasis

BioMed Research International ◽

10.1155/2018/6802637 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Paul T. King

Keyword(s):

Immune Response ◽

Inflammatory Response ◽

Respiratory Tract ◽

Lower Respiratory Tract ◽

Therapeutic Potential ◽

Small Airways ◽

Upper Respiratory Tract ◽

Causative Factors ◽

Triggering Factor

Bronchiectasis is a prevalent respiratory condition characterised by permanent and abnormal dilation of the lung airways (bronchi). There are a large variety of causative factors that have been identified for bronchiectasis; all of these compromise the function of the immune response to fight infection. A triggering factor may lead to the establishment of chronic infection in the lower respiratory tract. The bacteria responsible for the lower respiratory tract infection are usually found as commensals in the upper respiratory tract microbiome. The consequent inflammatory response to infection is largely responsible for the pathology of this condition. Both innate and adaptive immune responses are activated. The literature has highlighted the central role of neutrophils in the pathogenesis of bronchiectasis. Proteases produced in the lung by the inflammatory response damage the airways and lead to the pathological dilation that is the pathognomonic feature of bronchiectasis. The small airways demonstrate infiltration with lymphoid follicles that may contribute to localised small airway obstruction. Despite aggressive treatment, most patients will have persistent disease. Manipulating the immune response in bronchiectasis may potentially have therapeutic potential.

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