scholarly journals Cryptococcus neoformans Rim101 Is Associated with Cell Wall Remodeling and Evasion of the Host Immune Responses

mBio ◽  
2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Teresa R. O'Meara ◽  
Stephanie M. Holmer ◽  
Kyla Selvig ◽  
Fred Dietrich ◽  
J. Andrew Alspaugh
Keyword(s):  
Immune Response ◽  
Cell Wall ◽  
Transcription Factor ◽  
Immune System ◽  
Immune Responses ◽  
Cryptococcus Neoformans ◽  
Host Immune Response ◽  
Host Immune System ◽  
Content Type ◽  
Host Pathogen

ABSTRACTInfectious microorganisms often play a role in modulating the immune responses of their infected hosts. We demonstrate thatCryptococcus neoformanssignals through the Rim101 transcription factor to regulate cell wall composition and the host-pathogen interface. In the absence of Rim101,C. neoformansexhibits an altered cell surface in response to host signals, generating an excessive and ineffective immune response that results in accelerated host death. This host immune response to therim101Δ mutant strain is characterized by increased neutrophil influx into the infected lungs and an altered pattern of host cytokine expression compared to the response to wild-type cryptococcal infection. To identify genes associated with the observed phenotypes, we performed whole-genome RNA sequencing experiments under capsule-inducing conditions. We defined the downstream regulon of the Rim101 transcription factor and determined potential cell wall processes involved in the capsule attachment defects and altered mechanisms of virulence in therim101Δ mutant. The cell wall generates structural stability for the cell and allows the attachment of surface molecules such as capsule polysaccharides. In turn, the capsule provides an effective mask for the immunogenic cell wall, shielding it from recognition by the host immune system.IMPORTANCECryptococcus neoformansis an opportunistic human pathogen that is a significant cause of death in immunocompromised individuals. There are two major causes of death due to this pathogen: meningitis due to uncontrolled fungal proliferation in the brain in the face of a weakened immune system and immune reconstitution inflammatory syndrome characterized by an overactive immune response to subclinical levels of the pathogen. In this study, we examined howC. neoformansuses the conserved Rim101 transcription factor to specifically remodel the host-pathogen interface, thus regulating the host immune response. These studies explored the complex ways in which successful microbial pathogens induce phenotypes that ensure their own survival while simultaneously controlling the nature and degree of the associated host response.

scholarly journals Glycomaterials for probing host–pathogen interactions and the immune response

2016 ◽  
Vol 241 (10) ◽  
pp. 1042-1053 ◽  
Author(s):  
Mia L Huang ◽  
Christopher J Fisher ◽  
Kamil Godula
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Cell Surface ◽  
Host Response ◽  
Host Immune Response ◽  
Host Cells ◽  
Host Immune System ◽  
Host Pathogen Interactions ◽  
Host Pathogen ◽  
Functional Complexity

The initial engagement of host cells by pathogens is often mediated by glycan structures presented on the cell surface. Various components of the glycocalyx can be targeted by pathogens for adhesion to facilitate infection. Glycans also play integral roles in the modulation of the host immune response to infection. Therefore, understanding the parameters that define glycan interactions with both pathogens and the various components of the host immune system can aid in the development of strategies to prevent, interrupt, or manage infection. Glycomaterials provide a unique and powerful tool with which to interrogate the compositional and functional complexity of the glycocalyx. The objective of this review is to highlight some key contributions from this area of research in deciphering the mechanisms of pathogenesis and the associated host response.

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

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.

scholarly journals A Biofilm Matrix-Associated Protease Inhibitor ProtectsPseudomonas aeruginosafrom Proteolytic Attack

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Boo Shan Tseng ◽  
Courtney Reichhardt ◽  
Gennifer E. Merrihew ◽  
Sophia A. Araujo-Hernandez ◽  
Joe J. Harrison ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Protease Inhibitor ◽  
Neutrophil Elastase ◽  
Matrix Protein ◽  
Lipid Vesicles ◽  
Matrix Proteins ◽  
Host Immune System ◽  
Content Type ◽  
Biofilm Matrix

ABSTRACTPseudomonas aeruginosaproduces an extracellular biofilm matrix that consists of nucleic acids, exopolysaccharides, lipid vesicles, and proteins. In general, the protein component of the biofilm matrix is poorly defined and understudied relative to the other major matrix constituents. While matrix proteins have been suggested to provide many functions to the biofilm, only proteins that play a structural role have been characterized thus far. Here we identify proteins enriched in the matrix ofP. aeruginosabiofilms. We then focused on a candidate matrix protein, the serine protease inhibitor ecotin (PA2755). This protein is able to inhibit neutrophil elastase, a bactericidal enzyme produced by the host immune system duringP. aeruginosabiofilm infections. We show that ecotin binds to the key biofilm matrix exopolysaccharide Psl and that it can inhibit neutrophil elastase when associated with Psl. Finally, we show that ecotin protects both planktonic and biofilmP. aeruginosacells from neutrophil elastase-mediated killing. This may represent a novel mechanism of protection for biofilms to increase their tolerance against the innate immune response.IMPORTANCEProteins associated with the extracellular matrix of bacterial aggregates called biofilms have long been suggested to provide many important functions to the community. To date, however, only proteins that provide structural roles have been described, and few matrix-associated proteins have been identified. We developed a method to identify matrix proteins and characterized one. We show that this protein, when associated with the biofilm matrix, can inhibit a bactericidal enzyme produced by the immune system during infection and protect biofilm cells from death induced by the enzyme. This may represent a novel mechanism of protection for biofilms, further increasing their tolerance against the immune response. Together, our results are the first to show a nonstructural function for a confirmed matrix-interacting protein.

scholarly journals mSphere of Influence: Role of IRGM1 in Disease Control

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Sumanta Kumar Naik
Keyword(s):  
Immune Response ◽  
Quality Control ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Disease Control ◽  
Host Immune Response ◽  
Specific Interest ◽  
Mitochondrial Quality Control ◽  
Content Type

ABSTRACT Sumanta K. Naik works in the tuberculosis field, with a specific interest in the host immune response to Mycobacterium tuberculosis infection. In this mSphere of Influence article, he reflects on how the paper “IRGM1 links mitochondrial quality control to autoimmunity” by Prashant Rai et al. (Nat Immunol, 22:312–321, 2021, https://doi.org/10.1038/s41590-020-00859-0) impacted his research by revealing new roles for Irgm1 in immune responses.

scholarly journals Pleiotropic Effects of Cell Wall Amidase LytA on Streptococcus pneumoniae Sensitivity to the Host Immune Response

2014 ◽  
Vol 83 (2) ◽  
pp. 591-603 ◽  
Author(s):  
Elisa Ramos-Sevillano ◽  
Ana Urzainqui ◽  
Susana Campuzano ◽  
Miriam Moscoso ◽  
Fernando González-Camacho ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Wall ◽  
Streptococcus Pneumoniae ◽  
Complement Activation ◽  
Host Immune Response ◽  
Factor H ◽  
Pleiotropic Effects ◽  
Complement C3 ◽  
Classical Pathway ◽  
Content Type

The complement system is a key component of the host immune response for the recognition and clearance ofStreptococcus pneumoniae. In this study, we demonstrate that the amidase LytA, the main pneumococcal autolysin, inhibits complement-mediated immunity independently of effects on pneumolysin by a complex process of impaired complement activation, increased binding of complement regulators, and direct degradation of complement C3. The use of human sera depleted of either C1q or factor B confirmed that LytA prevented activation of both the classical and alternative pathways, whereas pneumolysin inhibited only the classical pathway. LytA prevented binding of C1q and the acute-phase protein C-reactive protein toS. pneumoniae, thereby reducing activation of the classical pathway on the bacterial surface. In addition, LytA increased recruitment of the complement downregulators C4BP and factor H to the pneumococcal cell wall and directly cleaved C3b and iC3b to generate degradation products. As a consequence, C3b deposition and phagocytosis increased in the absence of LytA and were markedly enhanced for thelytA plydouble mutant, confirming that a combination of LytA and Ply is essential for the establishment of pneumococcal pneumonia and sepsis in a murine model of infection. These data demonstrate that LytA has pleiotropic effects on complement activation, a finding which, in combination with the effects of pneumolysin on complement to assist with pneumococcal complement evasion, confirms a major role of both proteins for the full virulence of the microorganism during septicemia.

scholarly journals Immunity against Helminths: Interactions with the Host and the Intercurrent Infections

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Emmanuelle Moreau ◽  
Alain Chauvin
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Chronic Infection ◽  
Inflammatory Diseases ◽  
Economic Importance ◽  
Host Immune System ◽  
Helminth Parasites ◽  
Strong Immune Response ◽  
Helminth Infections

Helminth parasites are of considerable medical and economic importance. Studies of the immune response against helminths are of great interest in understanding interactions between the host immune system and parasites. Effector immune mechanisms against tissue-dwelling helminths and helminths localized in the lumen of organs, and their regulation, are reviewed. Helminth infections are characterized by an association of Th2-like and Treg responses. Worms are able to persist in the host and are mainly responsible for chronic infection despite a strong immune response developed by the parasitized host. Two types of protection against the parasite, namely, premune and partial immunities, have been described. Immune responses against helminths can also participate in pathogenesis. Th2/Treg-like immunomodulation allows the survival of both host and parasite by controlling immunopathologic disorders and parasite persistence. Consequences of the modified Th2-like responses on co-infection, vaccination, and inflammatory diseases are discussed.

scholarly journals Cross-Reactive Immune Responses as Primary Drivers of Malaria Chronicity

2013 ◽  
Vol 82 (1) ◽  
pp. 140-151 ◽  
Author(s):  
Eili Y. Klein ◽  
Andrea L. Graham ◽  
Manuel Llinás ◽  
Simon Levin
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Malaria Infection ◽  
Antigenic Variation ◽  
Cross Reactivity ◽  
Primary Response ◽  
Small Subset ◽  
Host Immune System ◽  
Primary Role ◽  
Content Type

ABSTRACTThe within-host dynamics of an infection with the malaria parasitePlasmodium falciparumare the result of a complex interplay between the host immune system and parasite. Continual variation of theP. falciparumerythrocyte membrane protein (PfEMP1) antigens displayed on the surface of infected red blood cells enables the parasite to evade the immune system and prolong infection. Despite the importance of antigenic variation in generating the dynamics of infection, our understanding of the mechanisms by which antigenic variation generates long-term chronic infections is still limited. We developed a model to examine the role of cross-reactivity in generating infection dynamics that are comparable to those of experimental infections. The hybrid computational model we developed is attuned to the biology of malaria by mixing discrete replication events, which mimics the synchrony of parasite replication and invasion, with continuous interaction with the immune system. Using simulations, we evaluated the dynamics of a single malaria infection over time. We then examined three major mechanisms by which the dynamics of a malaria infection can be structured: cross-reactivity of the immune response to PfEMP1, differences in parasite clearance rates, and heterogeneity in the rate at which antigens switch. The results of our simulations demonstrate that cross-reactive immune responses play a primary role in generating the dynamics observed in experimentally untreated infections and in lengthening the period of infection. Importantly, we also find that it is the primary response to the initially expressed PfEMP1, or small subset thereof, that structures the cascading cross-immune dynamics and allows for elongation of the infection.

scholarly journals Cysticercus cellulosae Regulates T-Cell Responses and Interacts With the Host Immune System by Excreting and Secreting Antigens

2021 ◽  
Vol 11 ◽  
Author(s):  
Xianmin Fan ◽  
Yue Zhang ◽  
Renhui Ouyang ◽  
Bo Luo ◽  
Lizhu Li ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Cytokine Production ◽  
Host Immune Response ◽  
Interleukin 10 ◽  
Host Immune System ◽  
Cell Responses ◽  
Cysticercus Cellulosae ◽  
T Cell Immune Responses

Cysticercus cellulosae (C. cellulosae) excretes and secretes antigens during the parasitic process to regulate the host immune response; however, resulting immune response and cytokine production in the host during infection still remains unclear. We used C. cellulosae crude antigens (CAs) as controls to explore the effect of excretory secretory antigens (ESAs) on T-cell immune responses in piglets. C. cellulosae ESAs induced imbalanced CD4+/CD8+ T-cell proportions, increased the CD4+Foxp3+ and CD8+Foxp3+ T-cell frequencies, and induced lymphocytes to produce interleukin-10, which was mainly attributed to CD4+ and CD4−CD8− T cells. The ESAs also induced Th2-type immune responses. The results showed that the ability of C. cellulosae to escape the host immune attacks and establish a persistent infection may be related to host immune response regulation by the ESAs.

scholarly journals Gut SymbiontsLactobacillus reuteriR2lc and 2010 Encode a Polyketide Synthase Cluster That Activates the Mammalian Aryl Hydrocarbon Receptor

2018 ◽  
Vol 85 (10) ◽  
Author(s):  
Mustafa Özçam ◽  
Restituto Tocmo ◽  
Jee-Hwan Oh ◽  
Amin Afrazi ◽  
Joshua D. Mezrich ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Immune System ◽  
Aryl Hydrocarbon Receptor ◽  
Gene Cluster ◽  
Polyketide Synthase ◽  
Lactobacillus Reuteri ◽  
Intestinal Inflammation ◽  
Host Immune System ◽  
Content Type ◽  
Aryl Hydrocarbon

ABSTRACTA mechanistic understanding of microbe-host interactions is critical to developing therapeutic strategies for targeted modulation of the host immune system. Different members of the gut symbiont speciesLactobacillus reuterimodulate host health by, for example, reduction of intestinal inflammation. Previously, it was shown thatL. reuteriactivates the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that plays an important role in the mucosal immune system, by the production of tryptophan catabolites. Here, we identified a novel pathway by whichL. reuteriactivates AhR, which is independent of tryptophan metabolism. We screened a library of 36 L. reuteristrains and determined that R2lc and 2010, strains with a pigmented phenotype, are potent AhR activators. By whole-genome sequencing and comparative genomics, we identified genes unique to R2lc and 2010. Our analyses demonstrated that R2lc harbors two genetically distinct polyketide synthase (PKS) clusters, functionally unknown (fun) andpks, each carried by a multicopy plasmid. Inactivation ofpks, but notfun, abolished the ability of R2lc to activate AhR.L. reuteri2010 has a gene cluster homologous to thepkscluster in R2lc with an identical gene organization, which is also responsible for AhR activation. In conclusion, we identified a novel PKS pathway inL. reuteriR2lc and 2010 that is responsible for AhR activation.IMPORTANCETemporary changes in the composition of the microbiota, for example, by oral administration of probiotics, can modulate the host immune system. However, the underlying mechanisms by which probiotics interact with the host are often unknown. Here, we show thatLactobacillus reuteriR2lc and 2010 harbor an orthologous PKS gene cluster that activates the aryl hydrocarbon receptor (AhR). AhR is a ligand-activated transcription factor that plays a key role in a variety of diseases, including amelioration of intestinal inflammation. Understanding the mechanism by which a bacterium modulates the immune system is critical for applying rational selection strategies for probiotic supplementation. Finally, heterologous and/or optimized expression of PKS is a logical next step toward the development of next-generation probiotics to prevent and treat disease.

scholarly journals Modulation of Host Immune Response Is an Alternative Strategy to Combat SARS-CoV-2 Pathogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Lakhveer Singh ◽  
Sakshi Bajaj ◽  
Manoj Gadewar ◽  
Nitin Verma ◽  
Mohd Nazam Ansari ◽  
...  
Keyword(s):  
Immune Response ◽  
Life Cycle ◽  
Immune System ◽  
Host Immune Response ◽  
Viral Rna ◽  
Host Cells ◽  
Spike Protein ◽  
Host Immune System ◽  
Host Membrane

The novel SARS-CoV-2virus that caused the disease COVID-19 is currently a pandemic worldwide. The virus requires an alveolar type-2 pneumocyte in the host to initiate its life cycle. The viral S1 spike protein helps in the attachment of the virus on toACE-2 receptors present on type-2 pneumocytes, and the S2 spike protein helps in the fusion of the viral membrane with the host membrane. Fusion of the SARS-CoV-2virus and host membrane is followed by entry of viral RNA into the host cells which is directly translated into the replicase-transcriptase complex (RTC) following viral RNA and structural protein syntheses. As the virus replicates within type-2 pneumocytes, the host immune system is activated and alveolar macrophages start secreting cytokines and chemokines, acting as an inflammatory mediator, and chemotactic neutrophils, monocytes, natural NK cells, and CD8+ T cells initiate the local phagocytosis of infected cells. It is not the virus that kills COVID-19 patients; instead, the aberrant host immune response kills them. Modifying the response from the host immune system could reduce the high mortality due to SARS-CoV-2 infection. The present study examines the viral life cycle intype-2 pneumocytes and resultant host immune response along with possible therapeutic targets.

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