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Frontiers in Immunology 2024Malaria remains a global health challenge, necessitating the development of effective vaccines. The RTS,S vaccination prevents (Pf) malaria but is ineffective against...
Malaria remains a global health challenge, necessitating the development of effective vaccines. The RTS,S vaccination prevents (Pf) malaria but is ineffective against (Pv) disease. Herein, we evaluated the murine immunogenicity of a recombinant PvCSP incorporating prevalent polymorphisms, adjuvanted with Alhydrogel or Poly I:C. Both formulations induced prolonged IgG responses, with IgG1 dominance by the Alhydrogel group and high titers of all IgG isotypes by the Poly I:C counterpart. Poly I:C-adjuvanted vaccination increased splenic plasma cells, terminally-differentiated memory cells (MBCs), and precursors relative to the Alhydrogel-combined immunization. Splenic B-cells from Poly I:C-vaccinated mice revealed an antibody-secreting cell- and MBC-differentiating gene expression profile. Biological processes such as antibody folding and secretion were highlighted by the Poly I:C-adjuvanted vaccination. These findings underscore the potential of Poly I:C to strengthen immune responses against Pv malaria.
Topics: Poly I-C; Plasmodium vivax; Immunity, Humoral; Immunity, Cellular; Protozoan Proteins; Malaria Vaccines; Aluminum Hydroxide; Immunoglobulin G; Male; Animals; Plasma Cells; Female; Mice, Inbred C57BL; Recombinant Proteins; Vaccination; Adjuvants, Vaccine; Immunogenicity, Vaccine; Malaria, Vivax
PubMed: 38650939
DOI: 10.3389/fimmu.2024.1331474 -
Journal of Pharmacological Sciences Dec 2020Pneumonia is a common illness that continues to be the major killer of remaining to be a significant source of morbidity and mortality in the patient population. Many...
Pneumonia is a common illness that continues to be the major killer of remaining to be a significant source of morbidity and mortality in the patient population. Many microorganisms cause pneumonia, and now concern is turning to the importance of the cause the new therapies for viral pneumonia. In the current study, we report the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on poly I: C-induced pneumonia. Andrographolide sulfonate was administrated through intraperitoneal injection to mice with poly I: C-induced pneumonia. Recruitment of airway inflammatory cells, alteration of lung histological induced by Poly I: C were significantly ameliorated by andrographolide sulfonate. The protein levels of pro-inflammatory cytokines in bronchoalveolar fluid (BALF) and serum were reduced by andrographolide sulfonate treatment. The levels of MUC5AC and MUC5B in lung tissue were also suppressed. These results reveal that andrographolide sulfate remarkably alleviated pneumonia induced by poly I:C in mice. Moreover, andrographolide sulfonate markedly inhibited the activation of nuclear factor-κB (NF-κB). Taken together, we demonstrated that andrographolide sulfonate ameliorated poly I: C-induced pneumonia in mice, suggesting the possible use of andrographolide sulfonate for virus-induced pneumonia in clinical.
Topics: Animals; Cytokines; Diterpenes; Inflammation Mediators; Injections, Intraperitoneal; Male; Mice, Inbred C57BL; Mucin 5AC; Mucin-5B; NF-kappa B; Phytotherapy; Pneumonia; Pneumonia, Viral; Poly I-C
PubMed: 33070837
DOI: 10.1016/j.jphs.2020.08.005 -
Frontiers in Immunology 2022Zika virus (ZIKV) is an emerging teratogenic arbovirus that persists in semen and is sexually transmitted. We previously demonstrated that ZIKV infects the human testis...
Zika virus (ZIKV) is an emerging teratogenic arbovirus that persists in semen and is sexually transmitted. We previously demonstrated that ZIKV infects the human testis and persists in testicular germ cells (TGCs) for several months after patients' recovery. To decipher the mechanisms underlying prolonged ZIKV replication in TGCs, we compared the innate immune response of human testis explants and isolated TGCs to ZIKV and to Poly(I:C), a viral RNA analog. Our results demonstrate the weak innate responses of human testis to both ZIKV and Poly(I:C) as compared with other tissues or species. TGCs failed to up-regulate antiviral effectors and type I IFN upon ZIKV or Poly(I:C) stimulation, which might be due to a tight control of PRR signaling, as evidenced by the absence of activation of the downstream effector IRF3 and elevated expression of repressors. Importantly, exogenous IFNβ boosted the innate immunity of TGCs and inhibited ZIKV replication in the testis , raising hopes for the prevention of ZIKV infection and persistence in this organ.
Topics: Antiviral Agents; Germ Cells; Humans; Male; Poly I-C; Testis; Zika Virus; Zika Virus Infection
PubMed: 35784373
DOI: 10.3389/fimmu.2022.909341 -
Journal of Visualized Experiments : JoVE Aug 2022Maternal immune activation (MIA) during pregnancy is consistently linked to increased risk of neurodevelopmental and neuropsychiatric disorders in offspring. Animal...
Maternal immune activation (MIA) during pregnancy is consistently linked to increased risk of neurodevelopmental and neuropsychiatric disorders in offspring. Animal models of MIA are used to test causality, investigate mechanisms, and develop diagnostics and treatments for these disorders. Despite their widespread use, many MIA models suffer from a lack of reproducibility and almost all ignore two important aspects of this risk factor: (i) many offspring are resilient to MIA, and (ii) susceptible offspring can exhibit distinct combinations of phenotypes. To increase reproducibility and model both susceptibility and resilience to MIA, the baseline immunoreactivity (BIR) of female mice before pregnancy is used to predict which pregnancies will result in either resilient offspring or offspring with defined behavioral and molecular abnormalities after exposure to MIA. Here, a detailed method of inducing MIA via intraperitoneal (i.p.) injection of the double stranded RNA (dsRNA) viral mimic poly(I:C) at 12.5 days of gestation is provided. This method induces an acute inflammatory response in the dam, which results in perturbations in brain development in mice that map onto similarly impacted domains in human psychiatric and neurodevelopmental disorders (NDDs).
Topics: Animals; Behavior, Animal; Disease Models, Animal; Female; Humans; Mice; Poly I-C; Pregnancy; Prenatal Exposure Delayed Effects; Reproducibility of Results
PubMed: 36063000
DOI: 10.3791/64095 -
American Journal of Reproductive... Nov 2018The contribution of fibroblasts to innate immune protection of the human female reproductive tract (FRT) against viral pathogens is relatively unknown.
PROBLEM
The contribution of fibroblasts to innate immune protection of the human female reproductive tract (FRT) against viral pathogens is relatively unknown.
METHOD OF STUDY
Endometrial (EM), endocervical (Cx) and ectocervical (ECx) fibroblasts were isolated from hysterectomy patients and grown in vitro. Fibroblasts were treated with the viral mimic poly (I:C) in the presence or absence of the sex hormone estradiol (E ), with gene expression measured by real-time RT-PCR and protein secretion by ELISA.
RESULTS
Poly (I:C) induced the expression of the interferon-stimulated genes (ISG) MxA, OAS2 and APOBEC3G, and the cytokines MCP-1, IL-8, IL-6, CCL20, IFNβ and RANTES by fibroblasts from all three sites. ISG upregulation was dependent upon Type I IFN signaling. E inhibited the poly (I:C)-induced upregulation of MxA and OAS2 in EM fibroblasts, but not Cx or ECx fibroblasts. E upregulated SDF-1α by EM fibroblasts but had no effect on secretion of other cytokines either alone or in the presence of poly (I:C). Conditioned media (CM) from poly (I:C)-treated or E -treated fibroblasts significantly reduced HIV infection of CD4+ T cells.
CONCLUSION
Stromal fibroblasts represent a level of innate immune protection against viral pathogens in the FRT beyond that seen with epithelial cells and immune cells. Our findings indicate that fibroblasts FRT are selectively responsive to E , capable of initiating an antiviral response against viral pathogens and may play a role in preventing HIV infection of CD4+ T cells.
Topics: Adult; Aged; Aged, 80 and over; Antigens, Viral; Cells, Cultured; Endometrium; Estradiol; Female; Fibroblasts; Humans; Immunity, Innate; Interferon Type I; Middle Aged; Poly I-C; Signal Transduction; Stromal Cells; Transcriptome; Virus Diseases
PubMed: 30295964
DOI: 10.1111/aji.13042 -
Scientific Reports Aug 2018Alopecia areata (AA) is a chronic, relapsing hair-loss disorder that is considered to be a T-cell-mediated autoimmune disease. Several animal models for AA have been...
Alopecia areata (AA) is a chronic, relapsing hair-loss disorder that is considered to be a T-cell-mediated autoimmune disease. Several animal models for AA have been created to investigate the pathophysiology and screen for effective therapeutic targets. As C3H/HeJ mice develop AA spontaneously in a low frequency, a novel animal model is needed to establish an AA-like condition faster and more conveniently. In this study, we present a novel non-invasive AA rodent model that avoids skin or lymph-node cell transfer. We simply injected C3H/HeJ mice subcutaneously with interferon-gamma (IFNγ) along with polyinosinic:polycytidylic acid (poly[I:C]), a synthetic dsRNA, to initiate innate immunity via inflammasome activation. Approximately 80% of the IFNγ and poly(I:C) co-injected mice showed patchy AA lesions after 8 weeks. None of the mice displayed hair loss in the IFNγ or poly(I:C) solely injection group. Immunohistochemical staining of the AA lesions revealed increased infiltration of CD4 and CD8 cells infiltration around the hair follicles. IFNγ and poly(I:C) increased the expression of NLRP3, IL-1β, CXCL9, CXCL10, and CXCL11 in mouse skin. Taken together, these findings indicate a shorter and more convenient means of AA animal model induction and demonstrate that inflammasome-activated innate immunity is important in AA pathogenesis.
Topics: Alopecia Areata; Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cells, Cultured; Chemokines, CXC; Disease Models, Animal; Drug Synergism; Female; Humans; Injections, Subcutaneous; Interferon-gamma; Interleukin-1beta; Mice; Mice, Inbred C3H; NLR Family, Pyrin Domain-Containing 3 Protein; Poly I-C
PubMed: 30131581
DOI: 10.1038/s41598-018-30997-3 -
Alcoholism, Clinical and Experimental... Sep 2020The inbred mouse strain C57BL/6 is widely used in both models of addiction and immunological disease. However, there are pronounced phenotypic differences in ethanol...
BACKGROUND
The inbred mouse strain C57BL/6 is widely used in both models of addiction and immunological disease. However, there are pronounced phenotypic differences in ethanol (EtOH) consumption and innate immune response between C57BL/6 substrains. The focus of this study was to examine the effects of substrain on innate immune response and neuroimmune-induced escalation of voluntary EtOH consumption. The main goal was to identify whether substrain differences in immune response can account for differences in EtOH behavior.
METHODS
We compared acute innate immune response with a viral dsRNA mimic, polyinosinic:polycytidylic acid (poly(I:C)), in brain using qRT-PCR in both C57BL/6N and C57BL/6J mice. Next, we used a neuroimmune model of escalation using poly(I:C) to compare drinking behavior between substrains. Finally, we compared brain neuroimmune response with both EtOH and repeated poly(I:C) in both substrains as a way to account for differences in EtOH behavior.
RESULTS
We found that C57BL/6 substrains have differing immune response and drinking behaviors. C57BL/6N mice have a shorter but more robust inflammatory response to acute poly(I:C). In contrast, C57BL/6J mice have a smaller but longer-lasting acute immune response to poly(I:C). In our neuroimmune-induced escalation model, C57BL/6J mice but not C57BL/6N mice escalate EtOH intake after poly(I:C). Finally, only C57BL/6J mice show enhanced proinflammatory transcript abundance after poly(I:C) and EtOH, suggesting that longer-lasting immune responses are critical to neuroimmune drinking phenotypes.
CONCLUSIONS
Altogether, this work has elucidated additional influences that substrain has on both innate immune response and drinking phenotypes. Our observations highlight the importance of considering and reporting the source and background used for production of transgenic and knockout mice. These data provide further evidence that genetic background must be carefully considered when investigating the role of neuroimmune signaling in EtOH abuse.
Topics: Alcohol Drinking; Animals; Behavior, Animal; Central Nervous System Depressants; Ethanol; Immunity, Innate; Interferon Inducers; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Mice, Transgenic; Models, Animal; Neuroimmunomodulation; Poly I-C
PubMed: 32640038
DOI: 10.1111/acer.14410 -
Frontiers in Immunology 2023Alloimmune responses against platelet antigens, which dominantly target the major histocompatibility complex (MHC), can cause adverse reactions to subsequent platelet...
INTRODUCTION
Alloimmune responses against platelet antigens, which dominantly target the major histocompatibility complex (MHC), can cause adverse reactions to subsequent platelet transfusions, platelet refractoriness, or rejection of future transplants. Platelet transfusion recipients include individuals experiencing severe bacterial or viral infections, and how their underlying health modulates platelet alloimmunity is not well understood.
METHODS
This study investigated the effect of underlying inflammation on platelet alloimmunization by modelling viral-like inflammation with polyinosinic-polycytidylic acid (poly(I:C)) or gram-negative bacterial infection with lipopolysaccharide (LPS), hypothesizing that underlying inflammation enhances alloimmunization. Mice were pretreated with poly(I:C), LPS, or nothing, then transfused with non-leukoreduced or leukoreduced platelets. Alloantibodies and allogeneic MHC-specific B cell (allo-B cell) responses were evaluated two weeks later. Rare populations of allo-B cells were identified using MHC tetramers.
RESULTS
Relative to platelet transfusion alone, prior exposure to poly(I:C) increased the alloantibody response to allogeneic platelet transfusion whereas prior exposure to LPS diminished responses. Prior exposure to poly(I:C) had equivalent, if not moderately diminished, allo-B cell responses relative to platelet transfusion alone and exhibited more robust allo-B cell memory development. Conversely, prior exposure to LPS resulted in diminished allo-B cell frequency, activation, antigen experience, and germinal center formation and altered memory B cell responses.
DISCUSSION
In conclusion, not all inflammatory environments enhance bystander responses and prior inflammation mediated by LPS on gram-negative bacteria may in fact curtail platelet alloimmunization.
Topics: Mice; Animals; Platelet Transfusion; Lipopolysaccharides; Poly C; Mice, Inbred BALB C; Histocompatibility Antigens; Inflammation; Poly I-C
PubMed: 38146372
DOI: 10.3389/fimmu.2023.1281130 -
Behavioural Brain Research Feb 2024Calorie restriction (CR) has been shown to extend the mean and maximum lifespan in both preclinical and clinical settings. We have previously demonstrated that CR...
Calorie restriction (CR) has been shown to extend the mean and maximum lifespan in both preclinical and clinical settings. We have previously demonstrated that CR attenuates lipopolysaccharide (LPS)-induced fever and sickness behavior. CR also leads to reductions in pro-inflammatory and increases in anti-inflammatory profiles. LPS is a bacterial mimetic; however, few studies have explored this phenomenon utilizing a viral mimetic, such as polyinosinic:polycytidylic acid (poly I:C). Dose-dependently, poly I:C induced an increase in core body temperature (T), with the largest dose (5000 µg/kg) resulting in a 1.62 °C ( ± 0.23 °C) T increase at 7 h post-injection in ad libitum mice and was associated with reduced home-cage locomotor activity. We then investigated the effect of 50% CR for 28 days to attenuate fever and sickness behavior induced by a poly I:C (5000 µg/kg) viral immune challenge. CR resulted in the partial attenuation of fever and sickness behavior measures post-poly I:C. The freely fed, control mice demonstrated a 2.02 °C ( ± 0.22 °C) increase in T at 7 h post-injection compared to the CR poly I:C group which demonstrated an increase in T of 0.94 °C ( ± 0.27 °C). Locomotor patterns post-injection were different, CR mice displayed a reduction in activity during the light phase, and the control group displayed a reduction during the dark phase. CR moderately attenuated the neuroinflammatory response with a reduction in microglial density in the ventromedial nucleus of the hypothalamus. The fever and sickness behavior attenuation seen after CR may be driven by similar anti-inflammatory processes as after LPS; however, further investigation is required.
Topics: Mice; Animals; Illness Behavior; Caloric Restriction; Lipopolysaccharides; Fever; Poly I-C; Anti-Inflammatory Agents
PubMed: 37838243
DOI: 10.1016/j.bbr.2023.114715 -
Microbes and Infection Sep 2022Viral respiratory infections caused by RNA viruses are one of the most important diseases around the world. The aim of this work was to study whether the nasal...
Viral respiratory infections caused by RNA viruses are one of the most important diseases around the world. The aim of this work was to study whether the nasal administration of non-viable Lactobacillus casei (LcM) was able to enhance respiratory antiviral defenses in young mice challenged with Poly I:C. Three-week-old BALB/c mice were nasally challenged with Poly I:C, used to mimic the pro-inflammatory state of lung infections caused by RNA viruses. LcM was nasally administered 2 days before Poly I:C challenge. Lactate dehydrogenase (LDH) activity, albumin concentration in broncho-alveolar lavages (BAL), wet-to-dry lung weight ratio, and total and differential leukocytes counts in blood were evaluated. Also, α, λ, γ interferons, IL-10, TNF-α, IL-4 in BAL and nasal lavages and total IgE in BAL and serum, were evaluated by ELISA. Poly I:C induced pulmonary injuries while alteration of bronchoalveolar-capillary barrier was reduced by nasal administration of LcM. Moreover, alterations in leukocyte counts induced by Poly I:C were regulated. LcM favorably modulated the cytokines responses triggered by Poly I:C challenge in nasal and lung mucosal compartments. Also, LcM decreased IgE levels in BAL and plasma compared with the Poly I:C group. LcM nasally administered reduced the lung damage induced by Poly I:C and prevented airway hyperreactivity.
Topics: Administration, Intranasal; Albumins; Animals; Antiviral Agents; Bronchoalveolar Lavage Fluid; Cytokines; Immunoglobulin E; Interferon-gamma; Interleukin-10; Interleukin-4; Lactate Dehydrogenases; Lacticaseibacillus casei; Lung; Mice; Mice, Inbred BALB C; Poly I-C; Tumor Necrosis Factor-alpha
PubMed: 35533988
DOI: 10.1016/j.micinf.2022.104997