scholarly journals Helicobacter pylori with a Truncated Lipopolysaccharide O Chain Fails To Induce Gastritis in SCID Mice Injected with Splenocytes from Wild-Type C57BL/6J Mice

2004 ◽  
Vol 72 (7) ◽  
pp. 3925-3931 ◽  
Author(s):  
K. A. Eaton ◽  
S. M. Logan ◽  
P. E. Baker ◽  
R. A. Peterson ◽  
M. A. Monteiro ◽  
...  
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Immune Responses ◽  
Scid Mice ◽  
Delayed Type Hypersensitivity ◽  
Wild Type ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Ifn Γ ◽  
H Pylori

ABSTRACT The goal of this study was to determine whether Helicobacter pylori lipopolysaccharide (LPS) O-chain polysaccharide contributes to gastritis in a mouse model. C57BL/6J or C57BL/6-Prkdcscid (severe combined immunodeficient [SCID]) mice were inoculated with H. pylori strain SS1 or SS1::0826kan, in which a β-1,4-galactosyltransferase (HP0826), an LPS biosynthetic enzyme, had been disrupted. H. pylori strain SS1::0826kan expresses truncated LPS lacking O chain. Recipient SCID mice were given C57BL/6J splenocytes by intraperitoneal injection. Bacterial colonization, gastric lesions (gastritis, neutrophilic infiltration, and gastric epithelial metaplasia), cellular (delayed-type hypersensitivity) and humoral immune responses to H. pylori sonicate, and gastric gamma interferon (IFN-γ) mRNA expression were quantified. Recipient SCID mice colonized by H. pylori strain SS1 developed extensive gastritis with loss of normal fundic gland morphology. In contrast, gastric mucosa of recipient SCID mice colonized by H. pylori strain SS1::0826kan was not statistically distinguishable from that of uninfected recipient mice. Delayed-type hypersensitivity and humoral immune responses were detected in infected mice inoculated with wild-type SS1, but not with SS1::0826kan. IFN-γ transcription was lower in mice infected with SS1::0826kan than in mice infected with SS1. In this model of rapidly progressive gastritis due to H. pylori, the O chain contributed to the extent of gastritis and to the host immune response. These data support a role for H. pylori LPS O chain in direct induction of the host immune response leading to gastritis and gastric damage and are in contrast to protein antigens, such as urease and cag products which do not contribute to gastritis in mice.

scholarly journals Cure of Helicobacter pylori Infection and Resolution of Gastritis by Adoptive Transfer of Splenocytes in Mice

2001 ◽  
Vol 69 (2) ◽  
pp. 1025-1031 ◽  
Author(s):  
Kathryn A. Eaton ◽  
Megan E. Mefford
Keyword(s):  
Helicobacter Pylori ◽  
Immune Responses ◽  
Adoptive Transfer ◽  
Host Response ◽  
Bacterial Colonization ◽  
Scid Mice ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
H Pylori ◽  
Cellular Immune

ABSTRACT Vaccination suppresses Helicobacter pylori colonization but does not cure infection. Furthermore, postvaccination gastritis, likely induced by enhanced host response to residual colonization, may exacerbate disease. The goal of this study was to determine if adoptive transfer of C57BL/6 splenocytes to C57BL/6scid/scid (severe combined immunodeficient [SCID]) mice cures infection without exacerbating gastritis. H. pylori-infected and uninfected C57BL/6 mice and SCID recipients of normal splenocytes were killed at intervals between 5 and 51 weeks after infection. Colonization and gastritis were quantified, humoral immune responses were determined by enzyme-linked immunosorbent assay, and cellular immune responses were determined by delayed-type hypersensitivity response and by a proliferative response of cultured splenocytes to H. pylorisonicate. In infected C57BL/6 mice, gastritis developed gradually and bacterial colonization diminished but persisted throughout the experiment. In contrast, gastritis in infected recipient SCID mice developed rapidly and bacterial colonization decreased precipitously. Gastritis in those mice peaked 9 weeks after adoptive transfer, however, and began to resolve. By 45 weeks after transfer, gastritis had returned to background levels and bacteria were no longer detectable. Resolution of gastritis and elimination of infection were associated with a cellular but not humoral immune response to H. pylori antigens. These results demonstrate that although the host response fails to clear bacterial colonization in normal mice, enhanced cellular immune responses in recipient SCID mice are capable of clearing H. pylori infection and allowing resolution of gastritis. Thus, immune mechanisms of cure exist, and effective and safe vaccination protocols may be feasible.

scholarly journals Role of Transcription Factor T-bet Expression by CD4+ Cells in Gastritis Due to Helicobacter pylori in Mice

2006 ◽  
Vol 74 (8) ◽  
pp. 4673-4684 ◽  
Author(s):  
Kathryn A. Eaton ◽  
Lucy H. Benson ◽  
Jennifer Haeger ◽  
Brian M. Gray
Keyword(s):  
T Cells ◽  
Helicobacter Pylori ◽  
Transcription Factor ◽  
Scid Mice ◽  
Delayed Type Hypersensitivity ◽  
Necrosis Factor Alpha ◽  
Ifn Γ ◽  
H Pylori ◽  
Cd4 Cell

ABSTRACT Gastritis due to Helicobacter pylori is induced by a Th1-mediated response that is CD4 cell and gamma interferon (IFN-γ) dependent. T-bet is a transcription factor that directs differentiation of and IFN-γ secretion by CD4+ Th1 T cells. The goal of this study was to use two mouse models to elucidate the role of T-bet in gastritis due to H. pylori. C57BL/6J mice, congenic T-bet knockout (KO) mutants, or congenic SCID (severe, combined immunodeficient) mutants were given live H. pylori by oral inoculation. SCID mice were given CD4+ splenocytes from C57BL/6J or T-bet KO mice by intraperitoneal injection. Twelve or 24 weeks after bacterial inoculation, C57BL/6J mice developed moderate gastritis but T-bet KO mice and SCID mice did not. In contrast, SCID recipients of either C57BL/6J T cells or T-bet KO T cells developed gastritis 4 or 8 weeks after adoptive transfer. In recipients of C57BL/6J CD4+ cells but not recipients of T-bet KO cells, gastritis was associated with a delayed-type hypersensitivity response to H. pylori antigen and elevated gastric and serum IFN-γ, interleukin 6, and tumor necrosis factor alpha. In spite of the absence of IFN-γ expression, indicating failure of Th1 differentiation, CD4+ T cells from T-bet KO mice induce gastritis in H. pylori-infected recipient SCID mice. This indicates that Th1-independent mechanisms can cause gastric inflammation and disease due to H. pylori.

scholarly journals Role of Gamma Interferon in Helicobacter pylori-Induced Gastric Inflammatory Responses in a Mouse Model

1999 ◽  
Vol 67 (1) ◽  
pp. 279-285 ◽  
Author(s):  
Naoki Sawai ◽  
Masakazu Kita ◽  
Tadashi Kodama ◽  
Toshihito Tanahashi ◽  
Yoshio Yamaoka ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Gene Knockout ◽  
Gamma Interferon ◽  
Gastric Epithelium ◽  
Wild Type ◽  
Ifn Γ ◽  
H Pylori

ABSTRACT The immune responses to Helicobacter pylori infection play important roles in gastroduodenal diseases. The contribution of gamma interferon (IFN-γ) to the immune responses, especially to the induction of gastric inflammation and to protection from H. pylori infection, was investigated with IFN-γ gene knockout (IFN-γ−/−) mice. We first examined the colonizing abilities of eight H. pylori strains with a short-term infection test in order to select H. pylori strains which could colonize the mouse stomach. Only three strains (ATCC 43504, CPY2052, and HPK127) colonized C57BL/6 wild-type mice, although all of the strains except for ATCC 51110 could colonize IFN-γ−/− mice. The number of H. pyloriorganisms colonizing the stomach in wild-type mice was lower than that in IFN-γ−/− mice. Oral immunization with the CPY2052 sonicate and cholera toxin protected against infection with strain CPY2052 in both types of mouse. These findings suggested that IFN-γ may play a protective role in H. pylori infection, although the degree of its protective ability was estimated to be low. In contrast, in a long-term infection test done to examine the contribution of IFN-γ to gastric inflammation, CPY2052-infected wild-type mice developed a severe infiltration of mononuclear cells in the lamina propria and erosions in the gastric epithelium 15 months after infection, whereas CPY2052-infected IFN-γ−/− mice showed no inflammatory symptoms. This result clearly demonstrated that IFN-γ plays an important role in the induction of gastric inflammation caused by H. pylori infection.

scholarly journals The Helicobacter pylori Autotransporter ImaA (HP0289) Modulates the Immune Response and Contributes to Host Colonization

2012 ◽  
Vol 80 (7) ◽  
pp. 2286-2296 ◽  
Author(s):  
William E. Sause ◽  
Andrea R. Castillo ◽  
Karen M. Ottemann
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Dependent Manner ◽  
Wild Type ◽  
Content Type ◽  
H Pylori ◽  
Murine Infections

ABSTRACTThe human pathogenHelicobacter pyloriemploys a diverse collection of outer membrane proteins to colonize, persist, and drive disease within the acidic gastric environment. In this study, we sought to elucidate the function of the host-induced geneHP0289, which encodes an uncharacterized outer membrane protein. We first generated an isogenicH. pylorimutant that lacksHP0289and found that the mutant has a colonization defect in single-strain infections and is greatly outcompeted in mouse coinfection experiments with wild-typeH. pylori. Furthermore, we used protease assays and biochemical fractionation coupled with an HP0289-targeted peptide antibody to verify that the HP0289 protein resides in the outer membrane. Our previous findings showed that theHP0289promoter is upregulated in the mouse stomach, and here we demonstrate thatHP0289expression is induced under acidic conditions in an ArsRS-dependent manner. Finally, we have shown that theHP0289mutant induces greater expression of the chemokine interleukin-8 (IL-8) and the cytokine tumor necrosis factor alpha (TNF-α) in gastric carcinoma cells (AGS). Similarly, transcription of the IL-8 homolog keratinocyte-derived chemokine (KC) is elevated in murine infections with the HP0289 mutant than in murine infections with wild-typeH. pylori. On the basis of this phenotype, we renamed HP0289 ImaA forimmunomodulatoryautotransporter protein. Our work has revealed that genes inducedin vivoplay an important role inH. pyloripathogenesis. Specifically, the outer membrane protein ImaA modulates a component of the host inflammatory response, and thus may allowH. pylorito fine tune the host immune response based on ImaA expression.

TLR4 regulates rabies virus-induced humoral immunity through recruitment of cDC2 to lymph organs

2021 ◽  
Author(s):  
Chen Chen ◽  
Chengguang Zhang ◽  
Haoqi Li ◽  
Zongmei Wang ◽  
Yueming Yuan ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Rabies Virus ◽  
Humoral Immunity ◽  
Humoral Immune Response ◽  
Critical Role ◽  
Wild Type ◽  
Humoral Immune ◽  
Specific Igg ◽  
Molecular Patterns

Rabies, caused by rabies virus (RABV), is fatal to both humans and animals around the world. Effective clinical therapy for rabies has not been achieved, and vaccination is the most effective means of preventing and controlling rabies. Although different vaccines, such as live attenuated and inactivated vaccines, can induce different immune responses, different expression of pattern recognition receptors (PRRs) also causes diverse immune responses. Toll-like receptor 4 (TLR4) is a pivotal PRR that induces cytokine production and bridges innate and adaptive immunity. Importantly, TLR4 recognizes various virus-derived pathogen-associated molecular patterns (PAMPs) and virus-induced damage-associated molecular patterns (DAMPs), usually leading to the activation of immune cells. However, the role of TLR4 in the humoral immune response induced by RABV has not been revealed yet. Based on TLR4-deficient ( TLR4 -/- ) and wild-type (WT) mouse models, we report that TLR4-dependent recruitment of the conventional type-2 dendritic cells (CD8α - CD11b + cDC2) into secondary lymph organs (SLOs) is critical for antigen presentation. cDC2-initiated differentiation of Tfh cells promotes the proliferation of germinal centre (GC) B cells, the formation of GCs, and the production of plasma cells (PCs), all of which contribute to the production of RABV-specific IgG and virus-neutralizing antibodies (VNAs). Collectively, our work demonstrates that TLR4 is necessary for the recruitment of cDC2 and for the induction of RABV-induced humoral immunity, which is regulated by the cDC2-Tfh-GC B axis. IMPORTANCE Vaccination is the most efficient method to prevent rabies. TLR4, a well-known immune sensor, plays a critical role in initiating innate immune response. Here, we found that TLR4 deficiency ( TLR4 -/- ) mice suppressed the induction of humoral immune response after immunization with rabies virus (RABV), including reduced production of VNAs and RABV-specific IgG, compared with that occurred in wild-type (WT) mice. As a consequence, TLR4 -/- mice exhibited higher mortality than WT mice after challenge with virulent RABV. Importantly, further investigation found that TLR4 signaling promoted the recruitment of cDC2 (CD8α + CD11b - ), a subset of cDCs known to induce CD4 + T cell immunity through their MHC-II presentation machinery. Our results imply that TLR4 is indispensable for an efficient humoral response to rabies vaccine, which provides new insight into the development of novel rabies vaccines.

scholarly journals Simulation Model for Dynamics of Dengue with Innate and Humoral Immune Responses

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
S. D. Perera ◽  
S. S. N. Perera
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Asymptomatic Infection ◽  
Severe Dengue ◽  
Viral Kinetics ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Kinetics Of

Dengue virus is a mosquito borne Flavivirus and the most prevalent arbovirus in tropical and subtropical regions around the world. The incidence of dengue has increased drastically over the last few years at an alarming rate. The clinical manifestation of dengue ranges from asymptomatic infection to severe dengue. Even though the viral kinetics of dengue infection is lacking, innate immune response and humoral immune response are thought to play a major role in controlling the virus count. Here, we developed a computer simulation mathematical model including both innate and adaptive immune responses to study the within-host dynamics of dengue virus infection. A sensitivity analysis was carried out to identify key parameters that would contribute towards severe dengue. A detailed stability analysis was carried out to identify relevant range of parameters that contributes to different outcomes of the infection. This study provides a qualitative understanding of the biological factors that can explain the viral kinetics during a dengue infection.

scholarly journals EFFECT OF BACILLUS OF CALMETTE-GUÉRIN, AVRIDINE AND Propionibacterium acnes AS IMMUNOMODULATORS ON RABIES IN MICE

1999 ◽  
Vol 41 (2) ◽  
pp. 107-114 ◽  
Author(s):  
J. MEGID ◽  
M.T.S. PERAÇOLI ◽  
P.R. CURI ◽  
C.R. ZANETTI ◽  
W.H. CABRERA ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Rabies Virus ◽  
Cellular Immune Response ◽  
Propionibacterium Acnes ◽  
Inoculation Test ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cellular Immune

The cellular and humoral immune responses of mice inoculated with rabies virus and treated with the Bacillus of Calmette-Guérin, Avridine and Propionibacterium acnes were evaluated in this paper. There was a higher percentage of surviving mice in groups submitted to P. acnes treatment. Lower levels of interferon-<FONT FACE="Symbol">g</font> (IFN-<FONT FACE="Symbol">g</font>) were found in infected mice. The intra-pad inoculation test (IPI) was not effective to detect cellular immune response, contrary to the results found in MIF reaction. The survival of mice did not present correlation with the levels of antirabies serum neutralizing (SN) antibodies titers, IFN-<FONT FACE="Symbol">g</font> concentration and MIF response.

scholarly journals Yersinia pestis caf1 Variants and the Limits of Plague Vaccine Protection

2008 ◽  
Vol 76 (5) ◽  
pp. 2025-2036 ◽  
Author(s):  
Lauriane E. Quenee ◽  
Claire A. Cornelius ◽  
Nancy A. Ciletti ◽  
Derek Elli ◽  
Olaf Schneewind
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Protective Immunity ◽  
Wild Type ◽  
Vaccine Protection ◽  
Subunit Vaccines ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Plague Vaccine ◽  
Highly Virulent

ABSTRACT Yersinia pestis, the highly virulent agent of plague, is a biological weapon. Strategies that prevent plague have been sought for centuries, and immunization with live, attenuated (nonpigmented) strains or subunit vaccines with F1 (Caf1) antigen is considered effective. We show here that immunization with live, attenuated strains generates plague-protective immunity and humoral immune responses against F1 pilus antigen and LcrV. Y. pestis variants lacking caf1 (F1 pili) are not only fully virulent in animal models of bubonic and pneumonic plague but also break through immune responses generated with live, attenuated strains or F1 subunit vaccines. In contrast, immunization with purified LcrV, a protein at the tip of type III needles, generates protective immunity against the wild-type and the fully virulent caf1 mutant strain, in agreement with the notion that LcrV can elicit vaccine protection against both types of virulent plague strains.

Mathematical modeling and analysis of innate and humoral immune responses to dengue infections

2019 ◽  
Vol 12 (07) ◽  
pp. 1950077 ◽  
Author(s):  
Sulanie Perera ◽  
S. S. N. Perera
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Steady State ◽  
Immune Responses ◽  
Dengue Virus ◽  
Innate Immune ◽  
Virus Dynamics ◽  
Quasi Steady State ◽  
Humoral Immune ◽  
Humoral Immune Responses

Dengue is an acute arthropode-borne virus, belonging to the family Flaviviridae. Currently, there are no vaccines or treatments available against dengue. Thus it is important to understand the dynamics of dengue in order to control the infection. In this paper, we study the long-term dynamics of the model that is presented in [S. D. Perera and S. S. N. Perera, Simulation model for dynamics of dengue with innate and humoral immune responses, Comput. Math. Methods Med. 2018 (2018) 8798057, 18 pp. https://doi.org/10.1155/2018/8798057 ] which describes the interaction of virus with infected and uninfected cells in the presence of innate and humoral immune responses. It was found the model has three equilibria, namely: infection free equilibrium, no immune equilibrium and endemic equilibrium, then analyzed its stability analytically. The analytical findings of each model have been exemplified by numerical simulations. Given the fact that intensity of dengue virus replication at early times of infection could determine clinical outcomes, it is important to understand the impact of innate immunity, which is believed to be the first line of defense against an invading pathogen. For this we carry out a simulation case study to investigate the importance of innate immune response on dengue virus dynamics. A comparison was done assuming that innate immunity was active; innate immunity was in quasi-steady state and innate immunity was inactive during the virus replication process. By a further analysis of the qualitative behavior of the quasi-steady state, it was observed that innate immune response plays a pivotal role in dengue virus dynamics. It can change the dynamical behavior of the system and is essential for the virus clearance.

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