Protective immunity to erythrocytic Plasmodium chabaudi AS infection involves IFNγ-mediated responses and a cellular infiltrate to the liver

Parasitology ◽  
2000 ◽  
Vol 121 (5) ◽  
pp. 473-482 ◽  
Author(s):  
P. BALMER ◽  
J. ALEXANDER ◽  
R. S. PHILLIPS
Keyword(s):  
Mortality Rate ◽  
Adoptive Transfer ◽  
Protective Immunity ◽  
No Reduction ◽  
Cytological Analysis ◽  
Plasmodium Chabaudi ◽  
Cellular Infiltrate ◽  
Specific Igg ◽  
Deficient Mice

IFNγ receptor (IFNγR) deficient mice and IL-4 deficient mice were infected with blood-stage Plasmodium chabaudi AS in order to analyse the role of Th1 (IFNγ) and Th2 (IL-4)-associated cytokines in the development of protective immunity to the parasite. A high mortality rate and failure to reduce the primary parasitaemia to subpatent levels was observed in the IFNγR deficient mice. IL-4 deficient mice controlled a primary P. chabaudi AS infection in a similar manner to control mice and no mortality was observed. IFNγR deficient mice had a reduction in parasite-specific IgG and a significantly increased level of total IgE compared to control mice. There was no reduction in the level of parasite-specific IgG in IL-4 deficient mice. Cytological analysis of the cells present in the spleen and liver during the primary parasitaemia revealed a reduction in the numbers of lymphocytes, monocytes and polymorphonuclear (PMN) cells in the liver at the peak of parasitaemia in both IFNγR deficient mice and IL-4 deficient mice compared to control mice. Adoptive transfer studies demonstrated that cells isolated from the liver at day 11 post-infection could confer some protective immunity to P. chabaudi AS infection.

scholarly journals Dissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Francesca Mancini ◽  
Gianmarco Gasperini ◽  
Omar Rossi ◽  
Maria Grazia Aruta ◽  
Maria Michelina Raso ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Critical Role ◽  
Shigella Sonnei ◽  
Added Value ◽  
Protein Antigens ◽  
Outer Membranes ◽  
O Antigen ◽  
Membrane Antigens ◽  
Specific Igg

AbstractGMMA are exosomes released from engineered Gram-negative bacteria resembling the composition of outer membranes. We applied the GMMA technology for the development of an O-Antigen (OAg) based vaccine against Shigella sonnei, the most epidemiologically relevant cause of shigellosis. S. sonnei OAg has been identified as a key antigen for protective immunity, and GMMA are able to induce anti-OAg-specific IgG response in animal models and healthy adults. The contribution of protein-specific antibodies induced upon vaccination with GMMA has never been fully elucidated. Anti-protein antibodies are induced in mice upon immunization with either OAg-negative and OAg-positive GMMA. Here we demonstrated that OAg chains shield the bacteria from anti-protein antibody binding and therefore anti-OAg antibodies were the main drivers of bactericidal activity against OAg-positive bacteria. Interestingly, antibodies that are not targeting the OAg are functional against OAg-negative bacteria. The immunodominant protein antigens were identified by proteomic analysis. Our study confirms a critical role of the OAg on the immune response induced by S. sonnei GMMA. However, little is known about OAg length and density regulation during infection and, therefore, protein exposure. Hence, the presence of protein antigens on S. sonnei GMMA represents an added value for GMMA vaccines compared to other OAg-based formulations.

scholarly journals IL-10-producing B cells regulate Th1/Th17-cell immune responses inPneumocystispneumonia

2019 ◽  
Vol 316 (1) ◽  
pp. L291-L301 ◽  
Author(s):  
Heng-Mo Rong ◽  
Ting Li ◽  
Chao Zhang ◽  
Dong Wang ◽  
Yang Hu ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Th17 Cell ◽  
Pneumocystis Pneumonia ◽  
Vital Role ◽  
Specific Igg ◽  
Pneumocystis Infection ◽  
Deficient Mice

Pneumocystis pneumonia (PCP) is a common opportunistic infectious disease that is prevalent in immunosuppressed hosts. Accumulating evidence shows that B cells play an important role in infectious diseases. In the present study, the immune regulatory role of mature B cells in host defense to Pneumocystis was evaluated. Pneumocystis infection resulted in a decrease in B cells in patients and mice, and the Pneumocystis burden in B cell-deficient mice also progressively increased from weeks 1 to 7 after infection. The clearance of Pneumocystis was delayed in B cell-activating factor receptor (BAFF-R)-deficient mice (BAFF-R−/−mice), which had few B cells and Pneumocystis-specific IgG and IgM antibodies, compared with clearance in wild-type (WT) mice. There were fewer effector CD4+T cells and higher percentages of T helper (Th)1/Th17 cells in BAFF-R−/−mice than in WT mice. Adoptive transfer of naive B cells, mRNA sequencing, and IL-1β neutralization experiments indicated that IL-1β is a likely determinant of the IL-10-producing B cell-mediated suppression of Th1/Th17-cell immune responses in BAFF-R−/−PCP mice. Our data indicated that B cells play a vital role in the regulation of Th cells in response to Pneumocystis infection.

scholarly journals Central Role of Endogenous Gamma Interferon in Protective Immunity against Blood-Stage Plasmodium chabaudi AS Infection

2000 ◽  
Vol 68 (8) ◽  
pp. 4399-4406 ◽  
Author(s):  
Zhong Su ◽  
Mary M. Stevenson
Keyword(s):  
Protective Immunity ◽  
Gamma Interferon ◽  
Blood Stage ◽  
No Production ◽  
Plasmodium Chabaudi ◽  
Spleen Cells ◽  
Parasite Antigen ◽  
Ifn Γ

ABSTRACT The role of endogenous gamma interferon (IFN-γ) in protective immunity against blood-stage Plasmodium chabaudi AS malaria was studied using IFN-γ gene knockout (GKO) and wild-type (WT) C57BL/6 mice. Following infection with 106 parasitized erythrocytes, GKO mice developed significantly higher parasitemia during acute infection than WT mice and had severe mortality. In infected GKO mice, production of interleukin 12 (IL-12) p70 and tumor necrosis factor alpha in vivo and IL-12 p70 in vitro by splenic macrophages was significantly reduced compared to that in WT mice and the enhanced nitric oxide (NO) production observed in infected WT mice was completely absent. WT and GKO mice had comparable numbers of total nucleated spleen cells and B220+ and Mac-1+spleen cells both before and after infection. Infected WT mice, however, had significantly more F4/80+, NK1.1+, and F4/80+Ia+ spleen cells than infected GKO mice; male WT had more CD3+ cells than male GKO mice. In comparison with those from WT mice, splenocytes from infected GKO mice had significantly higher proliferation in vitro in response to parasite antigen or concanavalin A stimulation and produced significantly higher levels of IL-10 in response to parasite antigen. Infected WT mice produced more parasite-specific immunoglobulin M (IgM), IgG2a, and IgG3 and less IgG1 than GKO mice. Significant gender differences in both GKO and WT mice in peak parasitemia levels, mortality, phenotypes of spleen cells, and proliferation of and cytokine production by splenocytes in vitro were apparent during infection. These results thus provide unequivocal evidence for the central role of endogenous IFN-γ in the development of protective immunity against blood-stage P. chabaudi AS.

scholarly journals Gamma Interferon Production by Cytotoxic T Lymphocytes Is Required for Resolution of Chlamydia trachomatis Infection

1998 ◽  
Vol 66 (11) ◽  
pp. 5457-5461 ◽  
Author(s):  
Mary F. Lampe ◽  
Christopher B. Wilson ◽  
Michael J. Bevan ◽  
Michael N. Starnbach
Keyword(s):  
Chlamydia Trachomatis ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Adoptive Transfer ◽  
Gamma Interferon ◽  
Chlamydia Trachomatis Infection ◽  
Immune Defect ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT In this study, we used mice in which the gene for gamma interferon (IFN-γ) has been disrupted (IFN-γ−/− mice) to study the role of this cytokine in the resolution of Chlamydia trachomatis infection. We show that IFN-γ−/− mice are impaired in the ability to clear infection with C. trachomatis compared to IFN-γ+/+ control mice. Activated CD8+ cytotoxic T lymphocytes (CTL) secrete IFN-γ in response to intracellular infection, and we have shown previously that a Chlamydia-specific CTL line can reduceC. trachomatis infection when adoptively transferred into infected mice. In the present study, we found that when these IFN-γ+/+ CTL lines are transferred intoChlamydia-infected IFN-γ−/− mice, the transferred CTL cannot overcome the immune defect seen in the IFN-γ−/− mice. We also show thatChlamydia-specific CTL can be cultured from IFN-γ-deficient mice infected with C. trachomatis; however, the adoptive transfer of IFN-γ−/− CTL into infected IFN-γ+/+ mice does not reduce the level of infection. These results suggest that IFN-γ production by CTL is not sufficient to overcome the defect that IFN-γ−/− mice have in the resolution of Chlamydia infection, yet IFN-γ production by CTL is required for the protective effect seen upon adoptive transfer of CTL into IFN-γ+/+ mice.

scholarly journals Short Communication: Some Observations on the Role of Bradykinin in Immunity toTeladorsagia circumcinctain Sheep

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Andrew R. Williams
Keyword(s):  
Smooth Muscle ◽  
Mast Cells ◽  
Muscle Contraction ◽  
Protective Immunity ◽  
Short Communication ◽  
Smooth Muscle Contraction ◽  
Teladorsagia Circumcincta ◽  
Specific Igg ◽  
Allergic Disorders

Bradykinin is a physiologically active peptide involved in vasodilation and smooth muscle contraction and is previously shown to be increased in gastrointestinal mucus during nematode challenge in sheep. Here, it is shown that bradykinin in the abomasum is positively correlated with both mast cells and globule leukocytes in the abomasum, and that all three of these parameters are negatively associated with numbers of adultTeladorsagia circumcinctaduring the challenge of immune sheep. It is suggested that bradykinin either stimulates the degranulation of mast cells, or is released during this degranulation process, or both. Multiple regression showed that almost 60% of the variation of in adultT. circumcinctacould be explained by two variables, bradykinin andT. circumcincta—specific IgG1in plasma. This provides further evidence that bradykinin may be a mechanism of protective immunity in sheep, although its involvement in asthma and other allergic disorders raises questions about its role in unwanted immunopathology.

scholarly journals Anamnestic Protective Immunity to Bacillus anthracis Is Antibody Mediated but Independent of Complement and Fc Receptors

2008 ◽  
Vol 76 (5) ◽  
pp. 2177-2182 ◽  
Author(s):  
Eric T. Harvill ◽  
Manuel Osorio ◽  
Crystal L. Loving ◽  
Gloria M. Lee ◽  
Vanessa K. Kelly ◽  
...  
Keyword(s):  
T Cell ◽  
Bacillus Anthracis ◽  
Adoptive Transfer ◽  
Protective Immunity ◽  
Fc Receptors ◽  
Immunodeficient Mice ◽  
Antibody Titers ◽  
Immunocompetent Mice ◽  
Induced Immunity ◽  
Deficient Mice

ABSTRACT The threat of bioterrorist use of Bacillus anthracis has focused urgent attention on the efficacy and mechanisms of protective immunity induced by available vaccines. However, the mechanisms of infection-induced immunity have been less well studied and defined. We used a combination of complement depletion along with immunodeficient mice and adoptive transfer approaches to determine the mechanisms of infection-induced protective immunity to B. anthracis. B- or T-cell-deficient mice lacked the complete anamnestic protection observed in immunocompetent mice. In addition, T-cell-deficient mice generated poor antibody titers but were protected by the adoptive transfer of serum from B. anthracis-challenged mice. Adoptively transferred sera were protective in mice lacking complement, Fc receptors, or both, suggesting that they operate independent of these effectors. Together, these results indicate that antibody-mediated neutralization provides significant protection in B. anthracis infection-induced immunity.

scholarly journals Role of Antibodies in Immunity to Bordetella Infections

2003 ◽  
Vol 71 (4) ◽  
pp. 1719-1724 ◽  
Author(s):  
Girish S. Kirimanjeswara ◽  
Paul B. Mann ◽  
Eric T. Harvill
Keyword(s):  
Mouse Model ◽  
Protective Immunity ◽  
Comparative Approach ◽  
Human Pathogens ◽  
Clinical Observations ◽  
Limited Efficacy ◽  
Antibody Titers ◽  
Rapid Clearance ◽  
Deficient Mice

ABSTRACT The persistence of Bordetella pertussis and B. parapertussis within vaccinated populations and the reemergence of associated disease highlight the need to better understand protective immunity. The present study examined host immunity to bordetellae and addressed potential concerns about the mouse model by using a comparative approach including the closely related mouse pathogen B. bronchiseptica. As previously observed with B. pertussis, all three organisms persisted throughout the respiratory tracts of B-cell-deficient mice, indicating that B cells are required for bacterial clearance. However, adoptively transferred antibodies rapidly cleared B. bronchiseptica but not human pathogens. These results obtained with the mouse model are consistent with human clinical observations, including the lack of correlation between antibody titers and protection, as well as the limited efficacy of intravenous immunoglobulin treatments against human disease. Together, this evidence suggests that the mouse model accurately reflects substantial differences between immunities to these organisms. Although both B. pertussis and B. parapertussis are more closely related to B. bronchiseptica than they are to each other, they share the ability to resist rapid clearance from the lower respiratory tract by adoptively transferred antibodies, an adaptation that correlates with their emergence as human pathogens that circulate within vaccinated populations.

scholarly journals Fetal Macrophages Exposed to Salmonella Antigens Elicit Protective Immunity Against Overwhelming Salmonella Challenge in A Murine Model

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 245
Author(s):  
Jeng-Chang Chen ◽  
Liang-Shiou Ou ◽  
Ming-Ling Kuo ◽  
Li-Yun Tseng ◽  
Hsueh-Ling Chang ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Adoptive Transfer ◽  
Protective Immunity ◽  
T Cell Development ◽  
Active Role ◽  
Postnatal Life ◽  
Serum Transfer ◽  
Microbial Antigen ◽  
Lymphocyte Transfer

Despite the evidence for fetal immunization following maternal infection, it remained a mystery how the fetal immune system was primed by vertically-transmitted pathogens or microbial antigens, especially before its full maturation. We previously demonstrated the capacity of fetal macrophages for endocytosing oncoprotein and allergens to bridge towards adaptive immunity in postnatal life. To investigate the immunological consequences of fetal contact with microbial antigens and the role of fetal macrophages in the defense against infection before T-cell development, we exposed gestational day 14 murine fetuses and their macrophages to flagellin and heat-killed Salmonella Typhimurium. Recipients with in utero exposure to Salmonella antigens or adoptive transfer of microbial antigen-loaded fetal macrophages were examined for immune responses to Salmonella antigens and resistance to virulent Salmonella challenge. Fetal exposure to microbial antigens or adoptive transfer of microbial antigen-loaded fetal macrophages could confer antigen-specific adaptive immunity. However, protective immunity against lethal Salmonella challenge was only granted to those receiving heat-killed Salmonella antigens, presenting as heightened recall responses of serum anti-lipopolysaccharide immunoglobulins and interferon-gamma. In immunized recipients surviving Salmonella challenge, their serum transfer to succeeding recipients provided immediate protection from lethal Salmonella challenge in preference to lymphocyte transfer, indicating a more active role of humoral immunity in the prevention of Salmonella invasiveness. Our study sheds insight on the role of fetal macrophages in immunogenicity to transplacental pathogens regardless of fetal lymphocyte maturity, paving the way for fetal macrophage therapies to enhance vaccine responsiveness or increase resistance to pathogenic microorganisms in perinatal life.

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