Obesity-induced Hyperleptinemia Improves Survival and Immune Response in a Murine Model of Sepsis

Abstract Background: Obesity is a growing health problem and associated with immune dysfunction. Sepsis is defined as systemic inflammatory response syndrome that occurs during infection. Excessive inflammation combined with immune dysfunction can lead to multiorgan damage and death. Methods: The authors investigated the influence of a class 1 obesity (body mass index between 30 and 34.9) on immune function and outcome in sepsis and the role of leptin on the immune response. The authors used a long-term high-fat-diet feeding model (12 weeks) on C57Bl/6 mice (n = 100) and controls on standard diet (n = 140) followed by a polymicrobial sepsis induced by cecal ligation and puncture. Results: The authors show that class 1 obesity is connected to significant higher serum leptin levels (data are mean ± SEM) (5.7 ± 1.2 vs. 2.7 ± 0.2 ng/ml; n = 5; P = 0.033) and improved innate immune response followed by significant better survival rate in sepsis (71.4%, n = 10 vs. 10%, n = 14; P < 0.0001). Additional sepsis-induced increases in leptin levels stabilize body temperature and are associated with a controlled immune response in a time-dependent and protective manner. Furthermore, leptin treatment of normal-weight septic mice with relative hypoleptinemia (n = 35) also significantly stabilizes body temperature, improves cellular immune response, and reduces proinflammatory cytokine response resulting in improved survival (30%; n = 10). Conclusions: Relative hyperleptinemia of class 1 obesity or induced by treatment is protective in sepsis. Leptin seems to play a regulatory role in the immune system in sepsis, and treatment of relative hypoleptinemia could offer a new way of an individual sepsis therapy.

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Comparable Long-Term Rabies Immunity in Foxes after IntraMuscular and Oral Application Using a Third-Generation Oral Rabies Virus Vaccine

Vaccines ◽

10.3390/vaccines9010049 ◽

2021 ◽

Vol 9 (1) ◽

pp. 49

Author(s):

Verena te Kamp ◽

Virginia Friedrichs ◽

Conrad M. Freuling ◽

Ad Vos ◽

Madlin Potratz ◽

...

Keyword(s):

Immune Response ◽

Rabies Virus ◽

Specific Binding ◽

Lethal Dose ◽

Genetically Engineered ◽

Routes Of Administration ◽

Safety Studies ◽

Oral Rabies Vaccine ◽

Cellular Immune

The live genetically-engineered oral rabies virus (RABV) variant SPBN GASGAS induces long-lasting immunity in foxes and protection against challenge with an otherwise lethal dose of RABV field strains both after experimental oral and parenteral routes of administration. Induction of RABV-specific binding antibodies and immunoglobulin isotypes (IgM, total IgG, IgG1, IgG2) were comparable in orally and parenterally vaccinated foxes. Differences were only observed in the induction of virus-neutralizing (VNA) titers, which were significantly higher in the parenterally vaccinated group. The dynamics of rabies-specific antibodies pre- and post-challenge (365 days post vaccination) suggest the predominance of type-1 immunity protection of SPBN GASGAS. Independent of the route of administration, in the absence of IgG1 the immune response to SPBN GAGAS was mainly IgG2 driven. Interestingly, vaccination with SPBN GASGAS does not cause significant differences in inducible IFN-γ production in vaccinated animals, indicating a relatively weak cellular immune response during challenge. Notably, the parenteral application of SPBN GASGAS did not induce any adverse side effects in foxes, thus supporting safety studies of this oral rabies vaccine in various species.

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The Cellular Immune Response to Rabies Vaccination: A Systematic Review

Vaccines ◽

10.3390/vaccines7030110 ◽

2019 ◽

Vol 7 (3) ◽

pp. 110 ◽

Cited By ~ 4

Author(s):

Overduin ◽

van Dongen ◽

Visser

Keyword(s):

Immune Response ◽

Cellular Immune Response ◽

Plasma Cells ◽

Primary Response ◽

Extensive Literature ◽

Registration Number ◽

Extensive Literature Search ◽

Cellular Immune ◽

Rabies Vaccination

The effectiveness of rabies vaccines is conventionally determined by serological testing. In addition to this assessment of humoral immunity, cellular immunity could help assess effectiveness and protection through a broad range of parameters. Therefore, this study aimed to systematically review all literature on the kinetics and composition of the cellular immune response to rabies vaccination in humans. A total of 1360 studies were identified in an extensive literature search. Twenty studies were selected for inclusion. In a primary response, plasma cells are detectable from day 7 to day 14, peaking at day 10. Memory B-cells appear from day 10 up to at least day 28. After revaccination, natural killer (NK) cells are the first detectable cellular parameters. Further research is required to assess cellular parameters in relation to long-term (serological) immunity. This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42019134416.

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Göttingen Minipigs as a Model to Evaluate Longevity, Functionality, and Memory of Immune Response Induced by Pertussis Vaccines

Frontiers in Immunology ◽

10.3389/fimmu.2021.613810 ◽

2021 ◽

Vol 12 ◽

Author(s):

Céline Vaure ◽

Véronique Grégoire-Barou ◽

Virginie Courtois ◽

Emilie Chautard ◽

Cyril Dégletagne ◽

...

Keyword(s):

Immune Response ◽

B Cells ◽

Vaccine Development ◽

Vaccination Schedule ◽

Memory B Cells ◽

Immune Memory ◽

Preclinical Model ◽

Göttingen Minipig ◽

Cellular Immune

Evaluation of the short-term and long-term immunological responses in a preclinical model that simulates the targeted age population with a relevant vaccination schedule is essential for human vaccine development. A Göttingen minipig model was assessed, using pertussis vaccines, to demonstrate that vaccine antigen-specific humoral and cellular responses, including IgG titers, functional antibodies, Th polarization and memory B cells can be assessed in a longitudinal study. A vaccination schedule of priming with a whole cell (DTwP) or an acellular (DTaP) pertussis vaccine was applied in neonatal and infant minipigs followed by boosting with a Tdap acellular vaccine. Single cell RNAsequencing was used to explore the long-term maintenance of immune memory cells and their functionality for the first time in this animal model. DTaP but not DTwP vaccination induced pertussis toxin (PT) neutralizing antibodies. The cellular immune response was also characterized by a distinct Th polarization, with a Th-2-biased response for DTaP and a Th-1/Th-17-biased response for DTwP. No difference in the maintenance of pertussis-specific memory B cells was observed in DTaP- or DTwP-primed animals 6 months post Tdap boost. However, an increase in pertussis-specific T cells was still observed in DTaP primed minipigs, together with up-regulation of genes involved in antigen presentation and interferon pathways. Overall, the minipig model reproduced the humoral and cellular immune responses induced in humans by DTwP vs. DTaP priming, followed by Tdap boosting. Our data suggest that the Göttingen minipig is an attractive preclinical model to predict the long-term immunogenicity of human vaccines against Bordetella pertussis and potentially also vaccines against other pathogens.

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Reduced schedule of human anti rabies immunization with Fuenzalida & Palacios vaccine

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46651989000100005 ◽

1989 ◽

Vol 31 (1) ◽

pp. 23-27 ◽

Cited By ~ 4

Author(s):

Carlos Roberto Zanetti ◽

Silvana Regina Favoretto ◽

Milene Silva Tino ◽

Avelino Albas ◽

Elizabeth Juliana G. Valentini ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Humoral Immune Response ◽

The Other ◽

Double Dose ◽

Humoral Immune ◽

Cellular Immune Responses ◽

Lymphoblastic Transformation ◽

Cellular Immune

The present study evaluates the humoral and cellular immune responses in 35 volunteers submited to short antirabies vaccination schedules with the Fuenzalida & Palacios vaccine based on the administration of doses on non consecutive days. The volunteers were divided into two groups. The first group received a total number of five doses given on days 0, 4, 7, 20 and 35. The other group received four doses, the first one being a double dose given on day 0 and than three other single doses on days 7, 20 and 35. The evaluation of humoral immune response was carried out by serum neutralization (SN) and indirect immunofluorescense (IIF) tests, while the cellular immune response was evaluated by lymphoblastic transformation assay (LTA) and skin test (ST). According to our results these reduced schedules elicited early and effective humoral and cellulafimmune responses to rabies antigen suggesting that new reduced schedules should be extensively studied in order to give the proper bases to the proposition of changes in the current long-term schedule.

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Long-term administration of galactoside-specific mistletoe lectin in an animal model: no protection against N -butyl- N -(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis in rats and no induction of a relevant local cellular immune response

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s004320050022 ◽

2000 ◽

Vol 126 (3) ◽

pp. 125-138 ◽

Cited By ~ 18

Author(s):

E. Kunze ◽

H. Schulz ◽

M. Adamek ◽

H.-J. Gabius

Keyword(s):

Immune Response ◽

Animal Model ◽

Urinary Bladder ◽

Cellular Immune Response ◽

Mistletoe Lectin ◽

Bladder Carcinogenesis ◽

Term Administration ◽

Cellular Immune

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Detection of long term cellular immune response to Japanese encephalitis vaccination using IFN-γ ELIspot assay

Journal of Medical Virology ◽

10.1002/jmv.24893 ◽

2017 ◽

Vol 89 (12) ◽

pp. 2235-2238

Author(s):

Amreen Zia ◽

Dharamveer Singh ◽

Swati Saxena ◽

Jyoti Umrao ◽

Manjari Baluni ◽

...

Keyword(s):

Immune Response ◽

Japanese Encephalitis ◽

Cellular Immune Response ◽

Elispot Assay ◽

Ifn Γ ◽

Cellular Immune

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Trained Innate Immunity by Repeated Low-Dose Lipopolysaccharide Injections Displays Long-Term Neuroprotective Effects

Mediators of Inflammation ◽

10.1155/2020/8191079 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Xiao-yan Zhou ◽

Rong Gao ◽

Jian Hu ◽

Da-peng Gao ◽

Yan-ling Liao ◽

...

Keyword(s):

Immune Response ◽

Low Dose ◽

Neurological Diseases ◽

Cecal Ligation ◽

Immune Memory ◽

Sham Operation ◽

Neuroprotective Effects ◽

Neurobehavioral Outcomes ◽

Sepsis Survivors

Disrupted immune response is an important feature of many neurodegenerative conditions, including sepsis-associated cognitive impairment. Accumulating evidence has demonstrated that immune memory occurs in microglia, which has a significant impact on pathological hallmarks of neurological diseases. However, it remains unclear whether immune memory can cause subsequent alterations in the brain immune response and affect neurobehavioral outcomes in sepsis survivors. In the present study, mice received daily intraperitoneal injection of low-dose lipopolysaccharide (LPS, 0.1 mg/kg) for three consecutive days to induce immune memory (immune tolerance) and then were subjected to sham operation or cecal ligation and puncture (CLP) 9 months later, followed by a battery of neurobehavioral and biochemical studies. Here, we showed that repeated low-dose LPS injection-induced immune memory protected mice from sepsis-induced cognitive and affective impairments, which were accompanied by significantly decreased brain proinflammatory cytokines and immune response. In conclusion, our study suggests that modulation of brain immune responses by repeated LPS injections confers neuroprotective effects by preventing overactivated immune response in response to subsequent septic insult.

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