scholarly journals Tricomponent Complex Loaded with a Mosquito-Stage Antigen of the Malaria Parasite Induces Potent Transmission-Blocking Immunity

2014 ◽  
Vol 21 (4) ◽  
pp. 561-569 ◽  
Author(s):  
Takeshi Arakawa ◽  
Takafumi Tsuboi ◽  
Jetsumon Sattabongkot ◽  
Kozue Sakao ◽  
Motomi Torii ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Malaria Parasite ◽  
Matrix Protein ◽  
B Lymphocyte ◽  
Large Fraction ◽  
Surface Protein ◽  
Content Type ◽  
Malaria Vaccines ◽  
Binding Avidity ◽  
Immunoglobulin Binding

ABSTRACTThe development of malaria vaccines is challenging, partly because the immunogenicity of recombinant malaria parasite antigens is low. We previously demonstrated that parasite antigens integrated into a tricomponent immunopotentiating complex increase antiparasitic immunity. In this study, the B domains of a group GStreptococcus(SpG) strain andPeptostreptococcus magnus(PpL) were used to evaluate whether vaccine efficacy is influenced by the type of immunoglobulin-binding domain (IBD) in the tricomponent complex. IBDs were fused to a pentameric cartilage oligomeric matrix protein (COMP) to increase the binding avidity of the complexes for their targets. The COMP-IBD fusion proteins generated (COMP-SpG and COMP-PpL and the previously constructed COMP-Z) bound a large fraction of splenic B lymphocytes but not T lymphocytes. These carrier molecules were then loaded with an ookinete surface protein ofPlasmodium vivax, Pvs25, by chemical conjugation. The administration of the tricomponent complexes to mice induced more Pvs25-specific serum IgG than did the unloaded antigen. The PpL complex, which exhibited a broad Ig-binding spectrum, conferred higher vaccine efficacy than did the Z or SpG complexes when evaluated with a membrane feed assay. This study demonstrates that this tricomponent immunopotentiating system, incorporating IBDs as the B-lymphocyte-targeting ligands, is a promising technology for the delivery of malaria vaccines, particularly when combined with an aluminum salt adjuvant.

scholarly journals Diversity Covering AMA1-MSP119Fusion Proteins as Malaria Vaccines

2013 ◽  
Vol 81 (5) ◽  
pp. 1479-1490 ◽  
Author(s):  
Bart W. Faber ◽  
Sumera Younis ◽  
Edmond J. Remarque ◽  
Roberto Rodriguez Garcia ◽  
Vanessa Riasat ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Fusion Proteins ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Immunological Study ◽  
Growth Inhibition Assay ◽  
Content Type ◽  
Apical Membrane Antigen 1 ◽  
Malaria Vaccines ◽  
Order Of Magnitude

ABSTRACTTo overcome polymorphism in the malaria vaccine candidatePlasmodium falciparumapical membrane antigen 1 (PfAMA1), fusion protein chimeras comprised of three diversity-covering (DiCo) PfAMA1 molecules (D1, D2, and D3) and two allelic variants of the C-terminal 19-kDa region of merozoite surface protein 1 (MSP119) (variants M1 and M2) were generated. A mixture of fusion proteins (D1M1/D2M2D3) and the D1M1D2M2D3 fusion were compared to a single-unit mixture (D1/D2/D3/M1) in an immunological study in groups of rabbits. Following immunization, titers of antibodies (Abs) against four naturally occurring PfAMA1 alleles were high for all groups, as were growth inhibition assay (GIA) levels against two antigenically distinct laboratory parasite strains. Fusion of AMA1 to MSP119did not suppress levels of antibodies against the AMA1 component. In addition, the breadth of antibody responses was unaffected. Anti-AMA1 antibodies were largely responsible for parasite growth inhibition, as shown in reversal-of-inhibition experiments by adding competing AMA1 antigen. For all groups, titration of the MSP119antigen into the GIA led to only a small decrease in parasite inhibition, although titers of antibodies against MSP119were increased 15-fold for the groups immunized with fusion proteins. GIA with affinity-purified anti-MSP119antibodies showed that the 50% inhibitory concentrations of the anti-MSP119antibody preparations were in the same order of magnitude for all animals tested, leading to the conclusion that fusing MSP119to PfAMA1 leads to a small but significant increase in functional antibody levels. This study shows that combination of multiple vaccine candidates in fusion proteins may lead to improved characteristics of the vaccine.

scholarly journals Vaccine Efficacy of Recombinant Plasmodium falciparumMerozoite Surface Protein 1 in Malaria-Naive, -Exposed, and/or -Rechallenged Aotus vociferans Monkeys

2000 ◽  
Vol 68 (3) ◽  
pp. 1418-1427 ◽  
Author(s):  
Andrea F. Egan ◽  
Michael J. Blackman ◽  
David C. Kaslow
Keyword(s):  
Vaccine Efficacy ◽  
Malaria Parasite ◽  
Surface Protein ◽  
Challenge Infection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Grade ◽  
T Cell Epitopes ◽  
Lethal Challenge ◽  
Antibody Titers ◽  
Parasite Challenge

ABSTRACT Protection against a lethal challenge infection of Plasmodium falciparum was elicited in malaria-naive Aotus vociferans monkeys by vaccination with the C terminus 19-kDa protein of the major merozoite surface protein (MSP-119) fused to tetanus toxoid universal T-cell epitopes P30 and P2. Three of four monkeys were protected against a 104-parasite challenge. Four monkeys were challenged with 105 parasites; one self-cured the infection, two were protected against high parasitemia (<2%) but were treated for severe anemia (hematocrit of <25%), and the fourth was not protected. In this model system, anemia appears to be a manifestation of incomplete protection (prolonged low-level parasitemia). Enzyme-linked immunosorbent assay (ELISA) antibody titers correlated with protection. Antibodies from some protected monkeys inhibited secondary processing of MSP-142to MSP-133 and MSP-119. To mimic the repeated reinfections seen in regions where malaria is endemic, a second malaria parasite challenge was administered 4 months later. All P30P2MSP-119-vaccinated monkeys were protected; thus, a single challenge infection may underestimate vaccine efficacy. ELISA antibody titers correlated with protection against a second infection but had decreased compared to the first challenge. As most target populations for asexual blood-stage malaria vaccines will have been exposed to malaria parasites, a malaria parasite-exposed monkey was vaccinated with P30P2MSP-119. This monkey was completely protected, while a malaria parasite-naive P30P2MSP-119-vaccinated monkey self-cured a low-grade parasitemia. Prior malaria parasite infection primed the production of anti-native MSP-119 antibodies, which were boosted by vaccination with recombinant P30P2MSP-119. Preliminary data suggest that immunogenicity studies of vaccines designed for malaria parasite-exposed populations should also be conducted in malaria parasite-exposed subjects.

scholarly journals Merozoite Surface Protein 1 from Plasmodium falciparum Is a Major Target of Opsonizing Antibodies in Individuals with Acquired Immunity against Malaria

2017 ◽  
Vol 24 (11) ◽  
Author(s):  
Anja Jäschke ◽  
Boubacar Coulibaly ◽  
Edmond J. Remarque ◽  
Hermann Bujard ◽  
Christian Epp
Keyword(s):  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Epidemiological Studies ◽  
Acquired Immunity ◽  
Serum Antibodies ◽  
Content Type ◽  
Merozoite Surface Protein 1 ◽  
Malaria Vaccines ◽  
Major Target

ABSTRACT Naturally acquired immunity against malaria is largely mediated by serum antibodies controlling levels of blood-stage parasites. A limited understanding of the antigenic targets and functional mechanisms of protective antibodies has hampered the development of efficient malaria vaccines. Besides directly inhibiting the growth of Plasmodium parasites, antibodies can opsonize merozoites and recruit immune effector cells such as monocytes and neutrophils. Antibodies against the vaccine candidate merozoite surface protein 1 (MSP-1) are acquired during natural infections and have been associated with protection against malaria in several epidemiological studies. Here we analyzed serum antibodies from semi-immune individuals from Burkina Faso for their potential (i) to directly inhibit the growth of P. falciparum blood stages in vitro and (ii) to opsonize merozoites and to induce the antibody-dependent respiratory burst (ADRB) activity of neutrophils. While a few sera that directly inhibited the growth of P. falciparum blood stages were identified, immunoglobulin G (IgG) from all individuals clearly mediated the activation of neutrophils. The level of neutrophil activation correlated with levels of antibodies to MSP-1, and affinity-purified MSP-1-specific antibodies elicited ADRB activity. Furthermore, immunization of nonhuman primates with recombinant full-size MSP-1 induced antibodies that efficiently opsonized P. falciparum merozoites. Reversing the function by preincubation with recombinant antigens allowed us to quantify the contribution of MSP-1 to the antiparasitic effect of serum antibodies. Our data suggest that MSP-1, especially the partially conserved subunit MSP-183, is a major target of opsonizing antibodies acquired during natural exposure to malaria. Induction of opsonizing antibodies might be a crucial effector mechanism for MSP-1-based malaria vaccines.

scholarly journals CD4+ T Lymphocytes from Calves Immunized withAnaplasma marginale Major Surface Protein 1 (MSP1), a Heteromeric Complex of MSP1a and MSP1b, Preferentially Recognize the MSP1a Carboxyl Terminus That Is Conserved among Strains

2001 ◽  
Vol 69 (11) ◽  
pp. 6853-6862 ◽  
Author(s):  
Wendy C. Brown ◽  
Guy H. Palmer ◽  
Harris A. Lewin ◽  
Travis C. McGuire
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Protective Immunity ◽  
B Lymphocyte ◽  
Surface Protein ◽  
Specific Response ◽  
Major Surface Protein ◽  
Ifn Γ ◽  
Major Surface ◽  
Lymphocyte Responses

ABSTRACT Native major surface protein 1 (MSP1) of the ehrlichial pathogenAnaplasma marginale induces protective immunity in calves challenged with homologous and heterologous strains. MSP1 is a heteromeric complex of a single MSP1a protein covalently associated with MSP1b polypeptides, of which at least two (designated MSP1F1 and MSP1F3) in the Florida strain are expressed. Immunization with recombinant MSP1a and MSP1b alone or in combination fails to provide protection. The protective immunity in calves immunized with native MSP1 is associated with the development of opsonizing and neutralizing antibodies, but CD4+ T-lymphocyte responses have not been evaluated. CD4+ T lymphocytes participate in protective immunity to ehrlichial pathogens through production of gamma interferon (IFN-γ), which promotes switching to high-affinity immunoglobulin G (IgG) and activation of phagocytic cells to produce nitric oxide. Thus, an effective vaccine for A. marginaleand related organisms should contain both T- and B-lymphocyte epitopes that induce a strong memory response that can be recalled upon challenge with homologous and heterologous strains. This study was designed to determine the relative contributions of MSP1a and MSP1b proteins, which contain both variant and conserved amino acid sequences, in stimulating memory CD4+ T-lymphocyte responses in calves immunized with native MSP1. Peripheral blood mononuclear cells and CD4+ T-cell lines from MSP1-immunized calves proliferated vigorously in response to the immunizing strain (Florida) and heterologous strains of A. marginale. The conserved MSP1-specific response was preferentially directed to the carboxyl-terminal region of MSP1a, which stimulated high levels of IFN-γ production by CD4+ T cells. In contrast, there was either weak or no recognition of MSP1b proteins. Paradoxically, all calves developed high titers of IgG antibodies to both MSP1a and MSP1b polypeptides. These findings suggest that in calves immunized with MSP1 heteromeric complex, MSP1a-specific T lymphocytes may provide help to MSP1b-specific B lymphocytes. The data provide a basis for determining whether selected MSP1a CD4+ T-lymphocyte epitopes and selected MSP1a and MSP1b B-lymphocyte epitopes presented on the same molecule can stimulate a protective immune response.

scholarly journals Circulating Gut-Homing (α4β7+) Plasmablast Responses against Shigella Surface Protein Antigens among Hospitalized Patients with Diarrhea

2016 ◽  
Vol 23 (7) ◽  
pp. 610-617 ◽  
Author(s):  
Anuradha Sinha ◽  
Ayan Dey ◽  
Giulietta Saletti ◽  
Pradip Samanta ◽  
Partha Sarathi Chakraborty ◽  
...  
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
Surface Protein ◽  
Protein Antigens ◽  
Magnetic Cell Sorting ◽  
Content Type ◽  
Recent Onset ◽  
Microbiological Methods ◽  
Stool Specimens ◽  
Antibody Secreting Cells

Developing countries are burdened withShigelladiarrhea. Understanding mucosal immune responses associated with naturalShigellainfection is important to identify potential correlates of protection and, as such, to design effective vaccines. We performed a comparative analysis of circulating mucosal plasmablasts producing specific antibodies against highly conserved invasive plasmid antigens (IpaC, IpaD20, and IpaD120) and two recently identified surface protein antigens,pan-Shigellasurfaceprotein antigen 1 (PSSP1) and PSSP2, common to all virulentShigellastrains. We examined blood and stool specimens from 37 diarrheal patients admitted to the Infectious Diseases & Beliaghata General Hospital, Kolkata, India. The etiological agent of diarrhea was investigated in stool specimens by microbiological methods and real-time PCR. Gut-homing (α4β7+) antibody-secreting cells (ASCs) were isolated from patient blood by means of combined magnetic cell sorting and two-color enzyme-linked immunosorbent spot (ELISPOT) assay. Overall, 57% (21 of 37) and 65% (24 of 37) of the patients were positive forShigellainfection by microbiological and real-time PCR assays, respectively. The frequency of α4β7+IgG ASC responders against Ipas was higher than that observed against PSSP1 or PSSP2, regardless of theShigellaserotype isolated from these patients. Thus, α4β7+ASC responses to Ipas may be considered an indirect marker ofShigellainfection. The apparent weakness of ASC responses to PSSP1 is consistent with the lack of cross-protection induced by naturalShigellainfection. The finding that ASC responses to IpaD develop in patients with recent-onset shigellosis indicates that such responses may not be protective or may wane too rapidly and/or be of insufficient magnitude.

scholarly journals A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalStreptococcus pneumoniaeChallenge

2018 ◽  
Vol 87 (3) ◽  
Author(s):  
Win-Yan Chan ◽  
Claire Entwisle ◽  
Giuseppe Ercoli ◽  
Elise Ramos-Sevillano ◽  
Ann McIlgorm ◽  
...  
Keyword(s):  
Heat Shock ◽  
Protein A ◽  
Surface Protein ◽  
Surface Proteins ◽  
Rabbit Serum ◽  
Protein Antigens ◽  
Content Type ◽  
Multiple Antigen ◽  
Bacterial Lysates ◽  
Chromatography Step

ABSTRACTCurrent vaccination againstStreptococcus pneumoniaeuses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared fromS. pneumoniaeTIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp; thought to be immune adjuvants). Proteomics and immunoblot analyses demonstrated that, compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognized protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply). Vaccination of rodents with MAV induced robust antibody responses to multiple serotypes, including nonpneumococcal conjugate vaccine serotypes. Homologous and heterologous strains ofS. pneumoniaewere opsonized after incubation in sera from vaccinated rodents. In mouse models, active vaccination with MAV significantly protected against pneumonia, while passive transfer of rabbit serum from MAV-vaccinated rabbits significantly protected against sepsis caused by both homologous and heterologousS. pneumoniaestrains. Direct comparison of MAV preparations made with or without the heat shock step showed no clear differences in protein antigen content and antigenicity, suggesting that the chromatography step rather than Hsp induction improved MAV antigenicity. Overall, these data suggest that the MAV approach may provide serotype-independent protection againstS. pneumoniae.

scholarly journals Cytokines, Antibodies, and Histopathological Profiles duringGiardiaInfection and Variant-Specific Surface Protein-Based Vaccination

2018 ◽  
Vol 86 (6) ◽  
pp. e00773-17 ◽  
Author(s):  
Marianela C. Serradell ◽  
Pablo R. Gargantini ◽  
Alicia Saura ◽  
Sergio R. Oms ◽  
Lucía L. Rupil ◽  
...  
Keyword(s):  
Specific Surface ◽  
Oral Vaccine ◽  
Surface Protein ◽  
Meriones Unguiculatus ◽  
Surface Proteins ◽  
Secretory Iga ◽  
Mesenteric Lymph Nodes ◽  
Content Type ◽  
Humoral Immune ◽  
Humoral Immune Responses

ABSTRACTGiardiasis is one of the most common human intestinal diseases worldwide. Several experimental animal models have been used to evaluateGiardiainfections, with gerbils (Meriones unguiculatus) being the most valuable model due to their high susceptibility toGiardiainfection, abundant shedding of cysts, and pathophysiological alterations and signs of disease similar to those observed in humans. Here, we report cytokine and antibody profiles both during the course ofGiardiainfection in gerbils and after immunization with a novel oral vaccine comprising a mixture of purified variant-specific surface proteins (VSPs). Transcript levels of representative cytokines of different immune profiles as well as macro- and microtissue alterations were assessed in Peyer's patches, mesenteric lymph nodes, and spleens. During infection, cytokine responses showed a biphasic profile: an early induction of Th1 (gamma interferon [IFN-γ], interleukin-1β [IL-1β], IL-6, and tumor necrosis factor [TNF]), Th17 (IL-17), and Th2 (IL-4) cytokines, together with intestinal alterations typical of inflammation, followed by a shift toward a predominant Th2 (IL-5) response, likely associated with a counterregulatory mechanism. Conversely, immunization with an oral vaccine comprising the entire repertoire of VSPs specifically showed high levels of IL-17, IL-6, IL-4, and IL-5, without obvious signs of inflammation. Both immunized and infected animals developed local (intestinal secretory IgA [S-IgA]) and systemic (serum IgG) humoral immune responses against VSPs; however, only infected animals showed evident signs of giardiasis. This is the first comprehensive report of cytokine expression and anti-Giardiaantibody production during infection and VSP vaccination in gerbils, a reliable model of the human disease.

scholarly journals Application of Genetic Studies to Flow Cytometry Data and Its Impact on Therapeutic Intervention for Autoimmune Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Valeria Orrù ◽  
Maristella Steri ◽  
Francesco Cucca ◽  
Edoardo Fiorillo
Keyword(s):  
Flow Cytometry ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Immune Cell ◽  
Disease Risk ◽  
Association Studies ◽  
Large Fraction ◽  
Surface Protein ◽  
Genome Wide Association Studies ◽  
Human Immune System

In recent years, systematic genome-wide association studies of quantitative immune cell traits, represented by circulating levels of cell subtypes established by flow cytometry, have revealed numerous association signals, a large fraction of which overlap perfectly with genetic signals associated with autoimmune diseases. By identifying further overlaps with association signals influencing gene expression and cell surface protein levels, it has also been possible, in several cases, to identify causal genes and infer candidate proteins affecting immune cell traits linked to autoimmune disease risk. Overall, these results provide a more detailed picture of how genetic variation affects the human immune system and autoimmune disease risk. They also highlight druggable proteins in the pathogenesis of autoimmune diseases; predict the efficacy and side effects of existing therapies; provide new indications for use for some of them; and optimize the research and development of new, more effective and safer treatments for autoimmune diseases. Here we review the genetic-driven approach that couples systematic multi-parametric flow cytometry with high-resolution genetics and transcriptomics to identify endophenotypes of autoimmune diseases for the development of new therapies.

scholarly journals Differential Spleen Remodeling Associated with Different Levels of Parasite Virulence Controls Disease Outcome in Malaria Parasite Infections

mSphere ◽  
2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Ximei Huang ◽  
Sha Huang ◽  
Lai Chun Ong ◽  
Jason Chu-Shern Lim ◽  
Rebecca Joan Mary Hurst ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Malaria Parasite ◽  
Parasite Clearance ◽  
Biomechanical Properties ◽  
Parasite Infection ◽  
Complex Interaction ◽  
Content Type ◽  
Key Factor ◽  
Infected Rbcs ◽  
Rbc Deformability

ABSTRACT The spleen and its response to parasite infection are important in eliminating parasites in malaria. By comparing P. yoelii parasite lines with different disease outcomes in mice that had either intact spleens or had had their spleens removed, we showed that upon parasite infection, the spleen exhibits dramatic changes that can affect parasite clearance. The spleen itself directly impacts RBC deformability independently of parasite genetics. The data indicated that the changes in the biomechanical properties of malaria parasite-infected RBCs are the result of the complex interaction between host and parasite, and RBC deformability itself can serve as a novel predictor of clinical outcome. The results also suggest that early responses in the spleen are a key factor directing the clinical outcome of an infection. Infections by malaria parasites can lead to very different clinical outcomes, ranging from mild symptoms to death. Differences in the ability of the spleen to deal with the infected red blood cells (iRBCs) are linked to differences in virulence. Using virulent and avirulent strains of the rodent malaria parasite Plasmodium yoelii, we investigated how parasite virulence modulates overall spleen function. Following parasite invasion, a difference in parasite virulence was observed in association with different levels of spleen morphology and iRBC rigidity, both of which contributed to enhanced parasite clearance. Moreover, iRBC rigidity as modulated by the spleen was demonstrated to correlate with disease outcome and thus can be used as a robust indicator of virulence. The data indicate that alterations in the biomechanical properties of iRBCs are the result of the complex interaction between host and parasite. Furthermore, we confirmed that early spleen responses are a key factor in directing the clinical outcome of an infection. IMPORTANCE The spleen and its response to parasite infection are important in eliminating parasites in malaria. By comparing P. yoelii parasite lines with different disease outcomes in mice that had either intact spleens or had had their spleens removed, we showed that upon parasite infection, the spleen exhibits dramatic changes that can affect parasite clearance. The spleen itself directly impacts RBC deformability independently of parasite genetics. The data indicated that the changes in the biomechanical properties of malaria parasite-infected RBCs are the result of the complex interaction between host and parasite, and RBC deformability itself can serve as a novel predictor of clinical outcome. The results also suggest that early responses in the spleen are a key factor directing the clinical outcome of an infection.

scholarly journals Epithelial Adhesion Mediated by Pilin SpaC Is Required for Lactobacillus rhamnosus GG-Induced Cellular Responses

2014 ◽  
Vol 80 (16) ◽  
pp. 5068-5077 ◽  
Author(s):  
Courtney S. Ardita ◽  
Jeffrey W. Mercante ◽  
Young Man Kwon ◽  
Liping Luo ◽  
Madelyn E. Crawford ◽  
...  
Keyword(s):  
Lactobacillus Rhamnosus ◽  
Surface Protein ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Critical Surface ◽  
Content Type ◽  
Epithelial Migration ◽  
Extracellular Signal ◽  
Nadph Oxidase 1 ◽  
Mitogen Activated Protein

ABSTRACTLactobacillus rhamnosusGG is a widely used probiotic, and the strain's salutary effects on the intestine have been extensively documented. We previously reported that strain GG can modulate inflammatory signaling, as well as epithelial migration and proliferation, by activating NADPH oxidase 1-catalyzed generation of reactive oxygen species (ROS). However, how strain GG induces these responses is unknown. Here, we report that strain GG's probiotic benefits are dependent on the bacterial-epithelial interaction mediated by the SpaC pilin subunit. By comparing strain GG to an isogenic mutant that lacks SpaC (strain GGΩspaC), we establish that SpaC is necessary for strain GG to adhere to gut mucosa, that SpaC contributes to strain GG-induced epithelial generation of ROS, and that SpaC plays a role in strain GG's capacity to stimulate extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in enterocytes. In addition, we show that SpaC is required for strain GG-mediated stimulation of cell proliferation and protection against radiologically inflicted intestinal injury. The identification of a critical surface protein required for strain GG to mediate its probiotic influence advances our understanding of the molecular basis for the symbiotic relationship between some commensal bacteria of the gut lumen and enterocytes. Further insights into this relationship are critical for the development of novel approaches to treat intestinal diseases.

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