scholarly journals Distinct Roles of CD28- and CD40 Ligand-Mediated Costimulation in the Development of Protective Immunity and Pathology during Chlamydia muridarum Urogenital Infection in Mice

2009 ◽  
Vol 77 (7) ◽  
pp. 3080-3089 ◽  
Author(s):  
Lili Chen ◽  
Wen Cheng ◽  
Pooja Shivshankar ◽  
Lei Lei ◽  
Xiaoyun Zhang ◽  
...  
Keyword(s):  
Primary Infection ◽  
Protective Immunity ◽  
Gene Knockout ◽  
Secondary Infection ◽  
Cd40 Ligand ◽  
Wild Type ◽  
Chlamydia Muridarum ◽  
Urogenital Infection ◽  
Costimulatory Signals ◽  
Deficient Mice

ABSTRACT Infection with Chlamydia muridarum in the mouse urogenital tract can induce both protective immunity and inflammatory pathologies, which has been used as a model for understanding the immune and pathogenic mechanisms of C. trachomatis infection. We compared the roles of CD28- and CD40 ligand (CD40L)-mediated costimulation in C. muridarum infection. Mice with CD28 or CD80/CD86 gene knockout (KO) displayed an infection course similar to that of wild-type mice during both primary and secondary infection, suggesting that CD28-mediated costimulation is not required for protection against C. muridarum infection. However, mice deficient in CD40L or CD40 displayed a prolonged infection course after primary or secondary infection, suggesting that CD40-CD40L costimulation plays an essential role in the development of anti-C. muridarum immunity. Interestingly, the CD28- or CD80/CD86-deficient mice displayed significantly lower levels of inflammatory pathologies in the upper genital tracts after primary infection, although the attenuation in inflammation was no longer significant during secondary infection. However, the CD40L or CD40 KO mice developed inflammatory pathologies as severe as those in wild-type mice following either primary or secondary infection despite the obvious deficits in adaptive immunity in these KO mice. The resistance of CD28 or CD80/CD86 KO mice to chlamydial infection correlated with production of gamma interferon, while the development of inflammatory pathologies in CD40L or CD40 KO mice correlated with the production of other proinflammatory cytokines in mouse urogenital tracts during the early stages of the infection. These observations together suggest that C. muridarum-induced protective immunity and inflammatory pathologies can be mediated by distinct costimulatory signals.

scholarly journals The Alopecia Areata Phenotype Is Induced by the Water Avoidance Stress Test In cchcr1-Deficient Mice

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 840
Author(s):  
Qiaofeng Zhao ◽  
Satoshi Koyama ◽  
Nagisa Yoshihara ◽  
Atsushi Takagi ◽  
Etsuko Komiyama ◽  
...  
Keyword(s):  
Alopecia Areata ◽  
Gene Knockout ◽  
Stress Test ◽  
Coiled Coil ◽  
Risk Haplotype ◽  
Gene Expression Microarray ◽  
Wild Type ◽  
Gene Knockout Mice ◽  
Deficient Mice ◽  
Gene Expression Microarray Analysis

We recently discovered a nonsynonymous variant in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene within the alopecia areata (AA) risk haplotype. We also reported that the engineered mice with this risk allele exhibited. To investigate more about the involvement of the CCHCR1 gene in AA pathogenesis, we developed an AA model using C57BL/6N cchcr1 gene knockout mice. In this study, mice (6–8 weeks) were divided into two groups: cchcr1−/− mice and wild-type (WT) littermates. Both groups were subjected to a water avoidance stress (WAS) test. Eight weeks after the WAS test, 25% of cchcr1−/− mice exhibited non-inflammatory foci of alopecia on the dorsal skin. On the other hand, none of wild-type littermates cause hair loss. The foci resembled human AA in terms of gross morphology, trichoscopic findings and histological findings. Additionally, gene expression microarray analysis of cchcr1−/− mice revealed abnormalities of hair related genes compared to the control. Our results strongly suggest that CCHCR1 is associated with AA pathogenesis and that cchcr1−/− mice are a good model for investigating AA.

scholarly journals Neutralization or Absence of the Interleukin-23 Pathway Does Not Compromise Immunity to Mycobacterial Infection

2006 ◽  
Vol 74 (11) ◽  
pp. 6092-6099 ◽  
Author(s):  
Alissa A. Chackerian ◽  
Shi-Juan Chen ◽  
Scott J. Brodie ◽  
Jeanine D. Mattson ◽  
Terrill K. McClanahan ◽  
...  
Keyword(s):  
Immune Response ◽  
Secondary Infection ◽  
Mycobacterial Infection ◽  
Effective Control ◽  
Bacterial Burden ◽  
Wild Type ◽  
Interleukin 23 ◽  
Deficient Mice ◽  
Stimulation Of

ABSTRACT Interleukin-23 (IL-23), a member of the IL-12 family, is a heterodimeric cytokine that is composed of the p40 subunit of IL-12 plus a unique p19 subunit. IL-23 is critical for autoimmune inflammation, in part due to its stimulation of the proinflammatory cytokine IL-17A. It is less clear, however, if IL-23 is required during the immune response to pathogens. We examined the role of IL-23 during Mycobacterium bovis BCG infection. We found that IL-23 reduces the bacterial burden and promotes granuloma formation when IL-12 is absent. However, IL-23 does not contribute substantially to host resistance when IL-12 is present, as the ability to control bacterial growth and form granulomata is not affected in IL-23p19-deficient mice and mice treated with a specific anti-IL-23p19 antibody. IL-23p19-deficient mice are also able to mount an effective memory response to secondary infection with BCG. While IL-23p19-deficient mice do not produce IL-17A, this cytokine is not necessary for effective control of infection, and antibody blocking of IL-17A in both wild-type and IL-12-deficient mice also has little effect on the bacterial burden. These data suggest that IL-23 by itself does not play an essential role in the protective immune response to BCG infection; however, the presence of IL-23 can partially compensate for the absence of IL-12. Furthermore, neutralization of IL-23 or IL-17A does not increase susceptibility to mycobacterial BCG infection.

scholarly journals Migration-Inhibitory Factor Gene-Deficient Mice Are Susceptible to Cutaneous Leishmania major Infection

2001 ◽  
Vol 69 (2) ◽  
pp. 906-911 ◽  
Author(s):  
Abhay R. Satoskar ◽  
Marcelo Bozza ◽  
Miriam Rodriguez Sosa ◽  
Guoshing Lin ◽  
John R. David
Keyword(s):  
Migration Inhibitory Factor ◽  
Protective Immunity ◽  
Leishmania Major ◽  
Inhibitory Factor ◽  
Interleukin 4 ◽  
Wild Type ◽  
Leishmanicidal Activity ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT To determine the role of endogenous migration-inhibitory factor (MIF) in the development of protective immunity against cutaneous leishmaniasis, we analyzed the course of cutaneous Leishmania major infection in MIF gene-deficient mice (MIF−/−) and wild-type (MIF+/+) mice. Following cutaneous L. major infection, MIF−/− mice were susceptible to disease and developed significantly larger lesions and greater parasite burdens than MIF+/+ mice. Interestingly, antigen-stimulated lymph node cells from MIF−/− mice produced more interleukin-4 (IL-4) and gamma interferon (IFN-γ) than those from MIF+/+ mice, although the differences were statistically not significant. IFN-γ-activated resting peritoneal macrophages from MIF−/− mice showed impaired macrophage leishmanicidal activity and produced significantly lower levels of nitric oxide and superoxide in vitro. The macrophages from MIF−/− mice, however, produced much more IL-6 than macrophages from wild-type mice. These findings demonstrate that endogenous MIF plays an important role in the development of protective immunity against L. majorin vivo. Furthermore, they indicate that the susceptibility of MIF−/− mice to L. major infection is due to impaired macrophage leishmanicidal activity rather than dysregulation of Th1 and Th2 responses.

scholarly journals Protective Immunity against Secondary Poxvirus Infection Is Dependent on Antibody but Not on CD4 or CD8 T-Cell Function

2006 ◽  
Vol 80 (13) ◽  
pp. 6333-6338 ◽  
Author(s):  
Vijay Panchanathan ◽  
Geeta Chaudhri ◽  
Gunasegaran Karupiah
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Primary Infection ◽  
Protective Immunity ◽  
Cell Function ◽  
Secondary Infection ◽  
Cd8 T Cell ◽  
Ectromelia Virus ◽  
T Cell Function

ABSTRACT Renewed interest in smallpox and the need for safer vaccines have highlighted our lack of understanding of the requirements for protective immunity. Since smallpox has been eradicated, surrogate animal models of closely related orthopoxviruses, such as ectromelia virus, have been used to establish critical roles for CD8 T cells in the control of primary infection. To study the requirements for protection against secondary infection, we have used a prime-challenge regime, in which avirulent ectromelia virus was used to prime mice that were then challenged with virulent ectromelia virus. In contrast to primary infection, T cells are not required for recovery from secondary infection, since gene knockout mice deficient in CD8 T-cell function and wild-type mice acutely depleted of CD4, CD8, or both subsets were fully protected. Protection correlated with effective virus control and generation of neutralizing antibody. Notably, primed mice that lacked B cells, major histocompatibility complex class II, or CD40 succumbed to secondary infection. Thus, antibody is essential, but CD4 or CD8 T cells are not required for recovery from secondary poxvirus infection.

scholarly journals B-Cell Deficiency Suppresses Vaccine-Induced Protection against Murine Filariasis but Does Not Increase the Recovery Rate for Primary Infection

2001 ◽  
Vol 69 (11) ◽  
pp. 7067-7073 ◽  
Author(s):  
Coralie Martin ◽  
Michael Saeftel ◽  
Phat N. Vuong ◽  
Simon Babayan ◽  
Kerstin Fischer ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Recovery Rate ◽  
Primary Infection ◽  
Subcutaneous Tissue ◽  
Interleukin 4 ◽  
Wild Type ◽  
Good Opportunity ◽  
Challenge Inoculation ◽  
Deficient Mice

ABSTRACT To establish the role of B cells and antibodies in destroying filariae, mice lacking mature B cells and therefore unable to produce antibodies were used. Litomosoides sigmodontis offers a good opportunity for this study because it is the only filarial species that completes its life cycle in mice. Its development was compared in B-cell-deficient mice (BALB/c μMT mice) and wild-type BALB/c mice in two different in vivo situations, vaccination with irradiated larvae and primary infection. In all cases, mice were challenged with subcutaneous inoculation of 40 infective larvae. Vaccine-induced protection was suppressed in B-cell-deficient mice. In these mice, eosinophils infiltrated the subcutaneous tissue normally during immunization; however, their morphological state did not change following challenge inoculation, whereas in wild-type mice the percentage of degranulated eosinophils was markedly increased. From this, it may be deduced that the eosinophil–antibody–B-cell complex is the effector mechanism of protection in vaccinated mice and that its action is fast and takes place in the subcutaneous tissue. In primary infection, the filarial survival and growth was not modified by the absence of B cells. However, no female worm had uterine microfilariae, nor did any mice develop a patent infection. In these mice, concentrations of type 1 (gamma interferon) and type 2 (interleukin-4 [IL-4], IL-5 and IL-10) cytokines in serum were lower and pleural neutrophils were more numerous. The effects of the μMT mutation therefore differ from those in B1-cell-deficient mice described on the same BALB/c background, which reveal a higher filarial recovery rate and microfilaremia. This outlines B2-cell-dependent mechanisms as favorable to the late maturation of L. sigmodontis.

scholarly journals Maintenance of neutralizing SARS-CoV-2 antibodies over five months in convalescent SARS-CoV-2 afflicted patients.

2020 ◽  
Author(s):  
Sissy Sonnleitner ◽  
Martina Prelog ◽  
Bainca Jansen ◽  
Chantal Rodgarkia-Dara ◽  
Sarah Gietl ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Primary Infection ◽  
Protective Immunity ◽  
Neutralization Assay ◽  
Immunofluorescence Assay ◽  
Crucial Importance ◽  
Wild Type ◽  
Specific Antibodies ◽  
Chemiluminescent Immunoassay ◽  
Type Infection

Level and duration of protective immunity against SARS-CoV-2 after primary infection is of crucial importance for preventive approaches. In order to provide evidence for the longevity of specific antibodies, we investigated the generation and maintenance of neutralizing antibodies of convalescent SARS-CoV-2-afflicted patients over a five month period post primary infection using an immunofluorescence assay, a commercial chemiluminescent immunoassay and an in-house enzyme-linked plaque-reduction neutralization assay. We present the successful application of an improved version of the plaque-reduction neutralization assay, which can be analyzed optometrically, significantly simplifying the interpretation of the results. Based on the results of the plaque-reduction neutralization assay, neutralizing antibodies were maintained in 85.3% of convalescent individuals without significant decay over five months. Furthermore, a positive correlation between severity of infection and neutralizing titer was shown. In conclusion, SARS-CoV-2-afflicted individuals have been proven to be able to establish and maintain neutralizing antibodies over a five months’ period after primary infection which allows to hope for long-lasting presumably protective humoral immunity after wild-type infection or even after vaccination.

scholarly journals Non-structural proteins of dengue 2 virus offer limited protection to interferon-deficient mice after dengue 2 virus challenge

2006 ◽  
Vol 87 (2) ◽  
pp. 339-346 ◽  
Author(s):  
Amanda E. Calvert ◽  
Claire Y.-H. Huang ◽  
Richard M. Kinney ◽  
John T. Roehrig
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Structural Proteins ◽  
Wild Type ◽  
Survival Times ◽  
E Proteins ◽  
Virus Challenge ◽  
E Protein ◽  
Low Levels ◽  
Deficient Mice

Chimeric (D2/WN) viruses containing the pre-membrane (prM) and envelope (E) proteins of West Nile virus (WN virus) and the capsid (C) and non-structural proteins of dengue 2 (DEN2) virus were used to evaluate the protective immunity elicited by either the flaviviral E protein or non-structural proteins. AG129 interferon-deficient mice, previously shown to be protected against lethal DEN1 or DEN2 viral infection after vaccination with a wild-type or candidate vaccine strain of DEN1 or DEN2 virus, respectively, were immunized with chimeric D2/WN virus and then challenged with DEN2 virus. D2/WN chimeric viruses were non-pathogenic in AG129 mice. These viruses elicited little anti-DEN E antibody, high levels of anti-DEN NS1 antibody and no or very low levels of DEN2 virus-neutralizing antibodies. Only 15 % of D2/WN-immunized mice survived challenge with DEN2 virus. However, their mean survival time increased by 11–14 days over non-immunized controls. These results suggest that, whilst the non-structural proteins were able to enhance mean survival times of AG129 mice, this protection was not as effective as protection mediated by the E protein.

scholarly journals Profiles of Th1 and Th2 Cytokines after Primary and Secondary Infection by Schistosoma mansoni in the Semipermissive Rat Host

1999 ◽  
Vol 67 (6) ◽  
pp. 2713-2719 ◽  
Author(s):  
Catherine Cêtre ◽  
Christine Pierrot ◽  
Cécile Cocude ◽  
Sophia Lafitte ◽  
André Capron ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Mrna Expression ◽  
Primary Infection ◽  
Protective Immunity ◽  
Egg Production ◽  
Secondary Infection ◽  
Mouse Strains ◽  
Th2 Response ◽  
Ifn Γ ◽  
Predominant Expression

ABSTRACT In contrast to most mouse strains, rats eliminate the primary schistosome burden around 4 weeks postinfection and subsequently develop protective immunity to reinfection. In rat schistosomiasis, we have shown predominant expression of a Th2-type cytokine response at the mRNA level after primary infection. In the present study, we showed a significant increase in interleukin-4 (IL-4) mRNA expression in inguinal lymph nodes early after a secondary infection. IL-5 mRNA expression showed a significant increase at days 2 and 4 postreinfection in the spleen and lymph nodes, respectively. We did not detect any gamma interferon (IFN-γ) mRNA after a challenge infection. Analysis of cytokine secretion by stimulated spleen cells after a primary infection showed predominant expression of IL-4 with maximum production on day 21, accompanied by production of IL-5 from day 11 to day 67. A significant increase in IFN-γ secretion was detected at day 21. Analysis of immunoglobulin G2b (IgG2b) and IgG2c (Th1-related isotypes) showed undetectable levels of IgG2b, but detectable levels of specific IgG2c antibodies were observed from day 42. The analysis of Th2-related isotypes showed high specific IgG1 and IgG2a antibody titers from day 29. After a secondary infection, only IL-4 and IL-5 secretion was sustained. This is supported by the increased production of Th2-related isotypes. These findings showed that S. mansoni infection can drive Th2 responses in rats in the absence of egg production which is required to induce a Th2 response in mice and are in favor of the role of Th2-type cytokines in protective immunity against reinfection.

In vitro oncospheral agglutination given by immune sera from mice infected, and rabbits injected, with eggs of Hymenolepis nana

Parasitology ◽  
1975 ◽  
Vol 71 (3) ◽  
pp. 465-473 ◽  
Author(s):  
Akira Ito
Keyword(s):  
Salt Solution ◽  
Primary Infection ◽  
Protective Immunity ◽  
Secondary Infection ◽  
Hymenolepis Nana ◽  
Intravenous Injections

Oncospheral agglutination given by sera immunized with Hymenolepisnana eggs is described as a new way of assessing H. nana infection. All sera of mice which possessed acquired protective immunity against reinfection by H. nana eggs had the potency to induce oncospheral agglutination in vitro. Only oncospheres, which had been hatched, agglutinated, no agglutination occurred in sera from uninfected mice. Oncospheral agglutination was carried out by mixing 0·1 ml of serial two-fold dilutions of serum and 0·1 ml of Hanks' balanced salt solution containing about 600 hatched oncospheres. Titre of agglutinins was indicated as a reciprocal of the final dilution capable of giving agglutination clusters made of three or more oncospheres. Agglutinins developed within 14 days after a primary infection with 500 shell-free eggs. There was no rapid increase of agglutinins within 4 days following a secondary infection. The titre increase coincided with the increase in dosages of eggs. Agglutinins were thought to be immunoglobulins, because the potency of the serum to agglutinate oncospheres was extinguished after absorption of globulins with rabbit anti-mouse globulin serum.Agglutinins were produced in rabbits by intravenous injections of shell-free eggs. The titres of the rabbit sera were much higher than those of mouse sera.

Protopolystoma xenopodis (Monogenea) primary and secondary infections in Xenopus laevis

Parasitology ◽  
2001 ◽  
Vol 123 (5) ◽  
pp. 455-463 ◽  
Author(s):  
J. A. JACKSON ◽  
R. C. TINSLEY
Keyword(s):  
Xenopus Laevis ◽  
Primary Infection ◽  
Protective Immunity ◽  
Egg Production ◽  
Secondary Infection ◽  
Reproductive Rate ◽  
Secondary Infections ◽  
Kinetics Of ◽  
Patent Infection

The reproductive kinetics of Protopolystoma xenopodis primary and secondary infections in Xenopus laevis were monitored in a 3-year study. Thirty-five naïve, lab-raised, full-sib X. laevis from 1 spawning were each exposed to 30 P. xenopodis eggs. The course of infections at 20 °C was monitored by screening isolated hosts for parasite egg production. Ninety-four percent of toads supported the development of gravid parasites. Infections became patent 9–19 weeks p.i., lasted 3–30 months and produced estimated totals of 1–7152 eggs/host. Variation in primary infection characters was discontinuous: a subgrouping of hosts (16%) was characterized by extended infection duration and low reproductive rate. In order to test the effect of long-term infection history on a subsequent challenge, each host was re-exposed to P. xenopodis infective stages (30 eggs/host) 6 months after the loss of its original infection. Establishment of patent infection was significantly lower (15%), and pre-patent period (12–28 weeks) longer, than in primary infections of the same hosts, and than in concurrently exposed naïve controls (contemporary full-sibs of the primary/secondary infection group, maintained in parallel; n = 28). There was no relationship between primary infection characteristics and secondary infection outcome. Overall reproductive output per initial infective stage for the primary exposure exceeded that for the secondary exposure by a ratio of 15[ratio ]1. Results suggest that primary infection with P. xenopodis can elicit strong, long-term protective immunity against re-infection in X. laevis.

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