Trained immunity is defined as an enhanced state of the innate system which leads to an improved immune response against related or non-related pathogens. Bacillus Calmette-Guérin (BCG) vaccine, a live attenuated Mycobacterium bovis strain, is currently one of the main inductors of trained immunity. The objective of the present study was to evaluate the protective effects of heat-inactivated M. bovis (HIMB) against Plasmodium berghei and Borrelia burgdorferi and characterize the immunological mechanisms involved. BALB/c and C3H/HeN mice were randomly assigned in similar number to either immunized group receiving two oral doses of HIMB with a 4-week interval, or control group treated with PBS. All the BALB/c mice were intraperitoneally infected with P. berghei while the C3H/HeN mice were subcutaneously infected with B. burgdorferi. Pathogen burden was significantly reduced in both immunized groups when compared to controls. The number of macrophages significantly decreased in the liver or in the spleen of the mice that had been immunized prior to the challenge with P. berghei or B. burgdorferi, respectively. Furthermore, the immunized groups showed an apparent upregulation of IFN-γ, TNF-α and IL-1α in the liver (P. berghei challenge) or a significant increase in IL-1α producing cells in the spleen (B. burgdorferi challenge). Our findings suggest that oral immunization with heat-inactivated mycobacteria limits pathogen burden through stimulation of the innate immune response in two vector-borne diseases in mice.

• MeSH
• adjuvancia imunologická * aplikace a dávkování   MeSH
• BCG vakcína * imunologie   aplikace a dávkování   MeSH
• Borrelia burgdorferi imunologie   MeSH
• cytokiny MeSH
• inaktivované vakcíny imunologie   aplikace a dávkování   MeSH
• interferon gama imunologie   MeSH
• interleukin-1alfa imunologie   MeSH
• játra imunologie   MeSH
• lymeská nemoc * prevence a kontrola   imunologie   MeSH
• makrofágy imunologie   MeSH
• malárie * prevence a kontrola   imunologie   MeSH
• Mycobacterium bovis * imunologie   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C3H MeSH
• myši MeSH
• Plasmodium berghei imunologie   MeSH
• protilátky bakteriální krev   MeSH
• slezina imunologie   mikrobiologie   MeSH
• TNF-alfa imunologie   MeSH
• vysoká teplota MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Tick-borne encephalitis virus (TBEV) is a tick-borne flavivirus that induces severe central nervous system disorders. It has recently raised concerns due to an expanding geographical range and increasing infection rates. Existing vaccines, though effective, face low coverage rates in numerous TBEV endemic regions. Our previous work demonstrated the immunogenicity and full protection afforded by a TBEV vaccine based on virus-like particles (VLPs) produced in Leishmania tarentolae cells in immunization studies in a mouse model. In the present study, we explored the impact of adjuvants (AddaS03TM, Alhydrogel®+MPLA) and administration routes (subcutaneous, intramuscular) on the immune response. Adjuvanted groups exhibited significantly enhanced antibody responses, higher avidity, and more balanced Th1/Th2 response. IFN-γ responses depended on the adjuvant type, while antibody levels were influenced by both adjuvant and administration routes. The combination of Leishmania-derived TBEV VLPs with Alhydrogel® and MPLA via intramuscular administration emerged as a highly promising prophylactic vaccine candidate, eliciting a robust, balanced immune response with substantial neutralization potential.

• MeSH
• adjuvancia imunologická * aplikace a dávkování   MeSH
• adjuvantní vakcína aplikace a dávkování   MeSH
• imunogenicita vakcíny MeSH
• injekce intramuskulární MeSH
• interferon gama imunologie   MeSH
• klíšťová encefalitida * prevence a kontrola   imunologie   MeSH
• Leishmania * imunologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• neutralizující protilátky krev   imunologie   MeSH
• protilátky virové * krev   imunologie   MeSH
• syntetické vakcíny * imunologie   aplikace a dávkování   MeSH
• Th1 buňky imunologie   MeSH
• virové vakcíny * imunologie   aplikace a dávkování   MeSH
• viry klíšťové encefalitidy * imunologie   MeSH
• VLP vakcíny * imunologie   aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Authors present a pilot study of the development of innovative flow cytometry-based assay with a potential for use in tuberculosis diagnostics. Currently available tests do not provide robust discrimination between latent tuberculosis infection (TBI) and tuberculosis disease (TB). The desired application is to distinguish between the two conditions by evaluating the production of a combination of three cytokines: IL-2 (interleukin-2), IFNɣ (interferon gamma) and TNFɑ (tumor necrosis factor alpha) in CD4+ and CD8+ T cells. The study was conducted on 68 participants, divided into two arms according to age (paediatric and adults). Each arm was further split into three categories (non-infection (NI), TBI, TB) based on the immune reaction to Mycobacterium tuberculosis (M.tb) after a close contact with pulmonary TB. Each blood sample was stimulated with specific M.tb antigens present in QuantiFERON tubes (TB1 and TB2). We inferred TBI or TB based on the predominant cytokine response of the CD4+ and/or CD8+ T cells. Significant differences were detected between the NI, TBI and the TB groups in TB1 in the CD4+TNFɑ+parameter in children. Along with IL-2, TNFɑ seems to be the most promising diagnostic marker in both CD4+and CD8+ T cells. However, more detailed analyses on larger cohorts are needed to confirm the observed tendencies.

• MeSH
• antigeny bakteriální imunologie   MeSH
• biologické markery krev   MeSH
• CD4-pozitivní T-lymfocyty * imunologie   MeSH
• CD8-pozitivní T-lymfocyty * imunologie   MeSH
• cytokiny krev   metabolismus   MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• dospělí MeSH
• interferon gama * krev   imunologie   MeSH
• interleukin-2 * krev   MeSH
• latentní tuberkulóza * diagnóza   imunologie   mikrobiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Mycobacterium tuberculosis * imunologie   MeSH
• pilotní projekty MeSH
• plicní tuberkulóza diagnóza   imunologie   mikrobiologie   krev   MeSH
• prediktivní hodnota testů MeSH
• předškolní dítě MeSH
• průtoková cytometrie * metody   MeSH
• senioři MeSH
• test pomocí interferonu gama metody   MeSH
• TNF-alfa krev   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Natural killer (NK) cells play a pivotal role in the immune response against viral infections, including SARS-CoV-2. However, our understanding of memory NK cell responses in the context of SARS-CoV-2 remains limited. To address this, we investigated the memory-like response of NK cells to SARS-CoV-2 peptides, presented by autologous cells. Blood samples from 45 donors underwent analysis for SARS-CoV-2 IgG antibodies, categorizing them into four groups based on the antibody kind and level. NK cells from SARS-CoV-2-experienced donors demonstrated enhanced degranulation and activation levels, IFNγ production and proliferative potential in response to SARS-CoV-2 peptides. Investigation of highly proliferating NK cells demonstrated the formation of distinct clusters depending on the SARS-CoV-2 peptide supplementation and the donor group. RNA sequencing revealed differential gene expression patterns, highlighting metabolism, protein transport, and immune response genes. Notably, KIR2DS4 expression correlated with enhanced IFNγ production, degranulation and proliferation levels, suggesting a role in SARS-CoV-2 recognition. Collectively, these findings provide detailed insights into antigen-specific NK cell responses to SARS-CoV-2 peptides, indicating potential mechanisms underlying NK cell activation in antiviral immunity.

• MeSH
• aktivace lymfocytů MeSH
• buňky NK * imunologie   MeSH
• COVID-19 * imunologie   MeSH
• degranulace buněk MeSH
• dospělí MeSH
• imunoglobulin G MeSH
• imunologická paměť MeSH
• interferon gama * imunologie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• protilátky virové krev   imunologie   MeSH
• receptory KIR genetika   metabolismus   MeSH
• SARS-CoV-2 * imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• interferon gama genetika   imunologie   MeSH
• Leishmania braziliensis imunologie   MeSH
• Leishmania donovani imunologie   MeSH
• Leishmania major imunologie   MeSH
• leishmanióza kožní imunologie   patologie   MeSH
• lidé MeSH
• makrofágy imunologie   MeSH
• monocyty imunologie   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• přirozená imunita genetika   imunologie   MeSH
• proteiny vázající GTP genetika   metabolismus   MeSH
• transkriptom genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Hematopoietic stem cell transplantation (HSCT) is a frequent therapeutic approach to restore hematopoiesis in patients with hematologic diseases. Patients receive a hematopoietic stem cell (HSC)-enriched donor cell infusion also containing immune cells, which may have a beneficial effect by eliminating residual neoplastic cells. However, the effect that donor innate immune cells may have on the donor HSCs has not been deeply explored. Here, we evaluate the influence of donor natural killer (NK) cells on HSC fate, concluded that NK cells negatively affect HSC frequency and function, and identified interferon-gamma (IFNγ) as a potential mediator. Interestingly, improved HSC fitness was achieved by NK cell depletion from murine and human donor infusions or by blocking IFNγ activity. Thus, our data suggest that suppression of inflammatory signals generated by donor innate immune cells can enhance engraftment and hematopoietic reconstitution during HSCT, which is particularly critical when limited HSC numbers are available and the risk of engraftment failure is high.

• MeSH
• buňky NK imunologie   metabolismus   MeSH
• dárci tkání * MeSH
• hematopoetické kmenové buňky imunologie   metabolismus   MeSH
• interferon gama genetika   imunologie   metabolismus   MeSH
• kokultivační techniky MeSH
• kultivované buňky MeSH
• lidé MeSH
• lymfocytární deplece metody   MeSH
• myši inbrední C57BL MeSH
• myši inbrední NOD MeSH
• myši knockoutované MeSH
• myši SCID MeSH
• myši transgenní MeSH
• přežívání štěpu genetika   imunologie   MeSH
• proteiny vázající zesilovač transkripce CCAAT genetika   imunologie   metabolismus   MeSH
• stanovení celkové genové exprese metody   MeSH
• transplantace hematopoetických kmenových buněk metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

The knowledge of mechanisms of regulation of IL-10 production by B cells remains still very limited. We show here that highly purified mouse B cells stimulated with LPS produce significant levels of IL-10, but Bregs in our model do not express detectable level of either Foxp3 or GATA-3. Nevertheless, IL-10 production by B cells is regulated by cytokines. In activated B cells, IL-10 production was significantly enhanced by IFN-γ and decreased in the presence of IL-4 or TGF-β. These findings are in sharp contrast with the observations in T cells, where IL-10 production correlates with GATA-3 or FoxP3 expression, and the cytokines regulate IL-10 production in a reverse manner than in activated B cells. These results thus show that the production of IL-10 by Bregs is regulated by cytokines independently of the expression of GATA-3 and FoxP3, which is clearly different from GATA-3-dependent IL-10 production by activated Th2 cells and FoxP3 expression in IL-10-producing Tregs.

• MeSH
• aktivace lymfocytů imunologie   MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa imunologie   MeSH
• forkhead transkripční faktory metabolismus   MeSH
• interferon gama imunologie   MeSH
• interleukin-10 biosyntéza   MeSH
• interleukin-4 imunologie   MeSH
• kultivované buňky MeSH
• lipopolysacharidy imunologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• regulační B-lymfocyty imunologie   MeSH
• regulační T-lymfocyty imunologie   MeSH
• Th2 buňky imunologie   MeSH
• transformující růstový faktor beta imunologie   MeSH
• transkripční faktor GATA3 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Hot water extract from biomass of heterotrophic mutant green alga Parachlorella kessleri HY1 (Chlorellaceae) was deproteinised, and three polysaccharidic fractions were obtained by preparative chromatography. The low-molecular fraction (1.5 × 104g mol-1) was defined mainly as branched O-2-β-xylo-(1→3)-β-galactofuranan where xylose is partially methylated at O-4. Two high-molecular fractions (3.05 × 105 and 9.84 × 104g mol-1) were complex polysaccharides containing α-l-rhamnan and xylogalactofuranan parts in different ratios. The polysaccharides were well soluble in hot water and, upon cooling, tended to self-segregate. Immunomodulatory activities of the obtained fractions were preliminary tested using ELISA, FACS and ImmunoSpot kits. The polysaccharides increased the TNF-α production in melanoma bearing mice with much higher intensity than in healthy mice. This was in agreement with the FACS results on T and B cells indicating their possibly secondary activation by innate immunity cells.

• MeSH
• B-lymfocyty účinky léků   imunologie   patologie   MeSH
• CD antigeny genetika   imunologie   MeSH
• Chlorophyta chemie   MeSH
• imunologické faktory chemie   izolace a purifikace   farmakologie   MeSH
• interferon gama genetika   imunologie   MeSH
• interleukin-2 genetika   imunologie   MeSH
• interleukin-4 genetika   imunologie   MeSH
• lipopolysacharidy antagonisté a inhibitory   farmakologie   MeSH
• melanom imunologie   patologie   MeSH
• metylace MeSH
• molekulová hmotnost MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádory kůže imunologie   patologie   MeSH
• polysacharidy chemie   izolace a purifikace   farmakologie   MeSH
• primární buněčná kultura MeSH
• regulace genové exprese účinky léků   MeSH
• rostlinné extrakty chemie   MeSH
• rozpustnost MeSH
• sacharidové sekvence MeSH
• T-lymfocyty účinky léků   imunologie   patologie   MeSH
• TNF-alfa genetika   imunologie   MeSH
• voda MeSH
• xylosa chemie   izolace a purifikace   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BI-VIDITEST Total r.t.u. (dále BIT) je test umožňující provést kultivaci nestimulovaných a PHA stimulovaných vzorků plné heparinizované krve. V supernatantech těchto kultur pak může být vhodnými metodami a soupravami stanovován IFNγ, ale i řada dalších cytokinů, chemokinů a růstových faktorů. BIT je tedy modifikací kultivační části testů IGRA (Interferon Gamma Releasing Assay), založených na analýze supernatantů buněčných kultur plné krve. Předpokládá se, že tento test bude postupně rozšiřován o testování buněčné reaktivity na řadu dalších stimulans.

BI-VIDITEST Total r.t.u. (next BIT) allows the cultivation of unstimulated and PHA-stimulated samples of whole heparinized blood to obtain the supernatants of these cultures. IFNγ, but also other cytokines, chemokines and growth factors can be determined by proper methods and kits in such supernatants. BIT is thus a modification of the cultivation part of Interferon Gamma Releasing Test (IGRA) based on analysis of blood culture supernatants. It is believed that this assay will be gradually expanded by testing responsiveness to a variety of other stimulants.

• Klíčová slova
• IGRA test, BI-VIDITEST,
• MeSH
• buněčná imunita * imunologie   MeSH
• imunologické testy * MeSH
• interferon gama imunologie   krev   MeSH
• klinické zkoušky jako téma MeSH
• kultivační vyšetření krve MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

In the majority of human tumors, downregulation of major histocompatibility complex class I (MHC‑I) expression contributes to the escape from the host immune system and resistance to immunotherapy. Relevant animal models are therefore needed to enhance the efficacy of cancer immunotherapy. As loss of β‑2 microglobulin expression results in irreversible downregulation of surface MHC‑I molecules in various human tumors, the β‑2 microglobulin gene (B2m) was deactivated in a mouse oncogenic TC‑1 cell line and a TC‑1/dB2m cell line that was negative for surface MHC‑I expression was derived. Following stimulation with interferon γ, MHC‑I heavy chains, particularly the H‑2Db molecules, were found to be expressed at low levels on the cell surface, but without β‑2 microglobulin. B2m deactivation in TC‑1/dB2m cells led to reduced proliferation and tumor growth. These cells were insensitive to DNA vaccination and only weakly responsive to combined immunotherapy with a DNA vaccine and the ODN1826 adjuvant. In vivo depletion demonstrated that NK1.1+ cells were involved in both reduced tumor growth and an antitumor effect of immunotherapy. The number of immune cells infiltrating TC‑1/dB2m‑induced tumors was comparable with that in tumors developing from TC‑1/A9 cells characterized by reversible MHC‑I downregulation. However, the composition of the cell infiltrate was different and, most importantly, infiltration with immune cells was not increased in TC‑1/dB2m tumors after immunotherapy. Therefore, the TC‑1/dB2m cell line represents a clinically relevant tumor model that may be used for enhancement of cancer immunotherapy.

• MeSH
• beta-2-mikroglobulin genetika   imunologie   MeSH
• cytotoxické T-lymfocyty imunologie   patologie   MeSH
• imunoterapie MeSH
• interferon gama imunologie   MeSH
• lidé MeSH
• MHC antigeny I. třídy genetika   imunologie   MeSH
• myši MeSH
• nádorové buněčné linie metabolismus   MeSH
• nádory genetika   imunologie   patologie   MeSH
• regulace genové exprese u nádorů genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH