Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses

Vaccination is a critical and reliable strategy for controlling the spread of influenza viruses in populations. Conventional seasonal split vaccines (SVs) for influenza evoke weaker immune responses than other types of vaccines, such as inactivated whole-virion vaccines, although SVs are highly safe compared to other types. Here, we assessed the potential of the lipid nanoparticle (LNP) we developed as an adjuvant for conventional influenza SV as an antigen in mice. The LNP did not induce the production of cytokines such as interleukin-6 (IL-6) and IL-12 p40 by dendritic cells or the expression of co-stimulatory molecules on these cells in vitro. In contrast, an SV adjuvanted with LNP improved SV-specific IgG1 and IgG2 responses and the Th1 response compared to the SV alone in mice. In addition, SV adjuvanted with an LNP gave superior protection against the influenza virus challenge over the SV alone and was as effective as SV adjuvanted with aluminum salts in mice. The LNP did not provoke inflammatory responses such as inflammatory cytokine production and inflammatory immune cell infiltration in mice, whereas aluminum salts induced inflammatory responses. These results suggest the potential of the LNP as an adjuvant without inflammatory responses for influenza SVs. Our strategy should be useful for developing influenza vaccines with enhanced efficacy and safety.

Download Full-text

Differential effects of lactobacilli on activation and maturation of mouse dendritic cells

Beneficial Microbes ◽

10.3920/bm2013.0066 ◽

2014 ◽

Vol 5 (3) ◽

pp. 323-334 ◽

Cited By ~ 10

Author(s):

I. Elawadli ◽

J.T. Brisbin ◽

B.A. Mallard ◽

M.W. Griffiths ◽

M. Corredig ◽

...

Keyword(s):

Dendritic Cells ◽

Lactic Acid ◽

Lactic Acid Bacteria ◽

Immune Responses ◽

Inflammatory Cytokine ◽

Cytokine Production ◽

Lactobacillus Helveticus ◽

Inflammatory Cytokine Production

Lactic acid bacteria (LAB) are of interest because of their potential to modulate immune responses. The effects of LAB range from regulation to stimulation of the immune system. A series of studies were performed in vitro to study the effects of six lactic acid bacteria (LAB), Lactobacillus helveticus LH-2, Lactobacillus acidophilus La-5, La-115, La-116 and La-14, and Lactobacillus salivarius, on maturation and activation of mouse dendritic cells. Production of tumour necrosis factor (TNF)-?, interleukin (IL)-6 and IL-10 by dendritic cells (DCs) was determined after treating cells with live LAB. The expression of DC maturation markers, CD80 and CD40, was also measured using flow cytometry after stimulation with LAB. In addition, the expression of Toll-like receptors (TLRs) 2, 4 and 9 by DCs stimulated with LAB was measured. Our results revealed that LAB act differentially on pro-inflammatory and anti-inflammatory cytokine production and induction of co-stimulatory molecules by DCs. Specifically, L. salivarius was found to be the most effective LAB to induce pro-inflammatory cytokine production and expression of co-stimulatory molecules. Moreover, La-14, La-116 and La-5 induced moderate maturation and activation of DCs. On the other hand, LH-2 and La-115 were the least effective lactobacilli to induce DC responses. The present study also revealed that L. salivarius was able to induce the expression of TLR2, 4 and 9 by DCs. In conclusion, various strains and species of LAB can differentially regulate DC activation and maturation, providing further evidence that these bacteria may have the ability to influence and steer immune responses in vivo.

Download Full-text

Immunostimulatory Effect of Zanthoxylum schinifolium-Based Complex Oil Prepared by Supercritical Fluid Extraction in Splenocytes and Cyclophosphamide-Induced Immunosuppressed Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/8107326 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Hak Yong Lee ◽

Young Mi Park ◽

Yang Hee Lee ◽

Yang Gyu Kang ◽

Hyang Man Lee ◽

...

Keyword(s):

Immune Responses ◽

Cytokine Production ◽

Nk Cell ◽

Cell Activity ◽

Pharmacological Activities ◽

Inflammatory Cytokine Production ◽

Immunostimulatory Effect ◽

Zanthoxylum Schinifolium

Complex oil of Zanthoxylum schinifolium and Perilla frutescens seed (ZPCO) is used as a traditional medicine due to its pharmacological activities. The aim of this study was to investigate the immunostimulatory effect of ZPCO in isolated splenocytes as well as in an immunosuppressed rat model, which was generated via oral administration of cyclophosphamide. Notably, our results showed that ZPCO exerted an immunity-enhancing effect both in vitro and in vivo. Specifically, ZPCO treatment enhanced the viability and inflammatory cytokine production of splenocytes and NK cell activity in vitro. Moreover, this product improved host defense under immunosuppressive conditions by increasing the number of immune cells and promoting the expression of cytokines involved in immune responses. Our results suggest that complex oil including Z. schinifolium should be explored as a novel immunostimulatory agent that could potentially be used for therapeutic purposes or as an ingredient in functional foods.

Download Full-text

Diazepam Impairs Innate and Adaptive Immune Responses and Ameliorates Experimental Autoimmune Encephalomyelitis

Frontiers in Immunology ◽

10.3389/fimmu.2021.682612 ◽

2021 ◽

Vol 12 ◽

Author(s):

Cristian R. Falcón ◽

Nicolás Fernández Hurst ◽

Ana Laura Vivinetto ◽

Pablo Héctor Horacio López ◽

Adolfo Zurita ◽

...

Keyword(s):

Immune Responses ◽

Inflammatory Cytokine ◽

Cytokine Production ◽

Clinical Signs ◽

Autoimmune Encephalomyelitis ◽

Adaptive Immune Responses ◽

Inflammatory Cytokine Production ◽

Adaptive Immune ◽

Experimental Autoimmune

Currently there is increasing attention on the modulatory effects of benzodiazepines on the immune system. Here, we evaluate how Diazepam (DZ) affects both innate and adaptive immunity. We observed that treatment with DZ and Lipopolysaccharide (LPS) on macrophages or dendritic cells (DCs) induced a defective secretion of IL-12, TNF-α, IL-6 and a lesser expression of classical activation markers as NO production and CD40 in comparison with LPS condition. More importantly, mice pre-treated with DZ and then challenged to LPS induced-septic shock showed reduced death. The DZ treatment shifted the LPS-induced pro-inflammatory cytokine production of peritoneal cells (PCs) to an anti-inflammatory profile commanded by IL-10. In agreement with this, DZ treatment prevented LPS-induced DC ability to initiate allogeneic Th1 and Th17 responses in vitro when compared with LPS-matured DC. Since these inflammatory responses are the key in the development of the experimental autoimmune encephalomyelitis (EAE), we treated EAE mice preventively with DZ. Mice that received DZ showed amelioration of clinical signs and immunological parameters of the disease. Additionally, DZ reduced the release of IFN-γ and IL-17 by splenocytes from untreated sick mice in vitro. For this reason, we decided to treat diseased mice therapeutically with DZ when they reached the clinical score of 1. Most importantly, this treatment ameliorated clinical signs, reduced the MOG-specific inflammatory cytokine production and prevented axonal damage. Altogether, these results indicate that DZ is a potent immunomodulator capable of controlling undesired innate and adaptive immune responses, both at the beginning of these responses and also once they have started.

Download Full-text

A15 MICROBES MEDIATE FIBER-INDUCED INFLAMMATION IN IBD

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.014 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 17-19

Author(s):

H Armstrong ◽

R Dickner ◽

A Rieger ◽

I K Mander ◽

J Jerasi ◽

...

Keyword(s):

Immune Cells ◽

Inflammatory Cytokine ◽

Cytokine Production ◽

Inflammatory Responses ◽

Ex Vivo ◽

Receptor Expression ◽

Dietary Fibers ◽

Microbial Composition ◽

Inflammatory Cytokine Production

Abstract Background The etiology of inflammatory bowel diseases (IBD) remains unknown, although gut microorganisms and diet have been implicated. Dietary fibers pass through the bowel undigested and are fermented within the intestine by microbes, promoting gut health. However, many IBD patients describe experiencing sensitivity to fibres. Interestingly, fiber receptors on immune cells are able to interact with fibers typically found on the surface of fungal cells (which share properties with dietary fibers), for example, resulting in a paradoxical pro-inflammatory response. Aims As an altered microbial composition is a hallmark of IBD, we hypothesized that the loss of fiber fermenting-microbes populating the IBD gut could lead to dietary fibers not being efficiently broken down into their beneficial biproducts, resulting in binding of intact fibers to pro-inflammatory host cell receptors. This can ultimately drive pro-inflammatory responses and a microenvironment that promotes continued dysbiosis and increased pathogenicity of select microbes, as observed in IBD. Methods Fiber receptor expression gut was examined using immunohistochemistry and flow cytometry and demonstrated elevated receptor expression due to increased presence of immune cells in IBD patient biopsies. Cytokine secretion, in response to fiber (5mg/mL) or pre-fermented fibers, cultured with microbes of interest, was measured by ELISAs in cell lines in vitro and biopsy tissues cultured ex vivo. Results Whole-fibers induced pro-inflammatory cytokine production in macrophage, monocytes, and neutrophils. Specific microbes were capable of fermenting fiber, measured by gas chromatography. Pre-fermentation of fibers by these microbes reduced inflammatory cytokine production. The fiber oligofructose increased IL-1β in pediatric CD (n=44) and UC (n=29) biopsies cultured ex vivo but not in non-IBD (n=25). The increase was greater in patients with more severe disease. Pre-fermentation of oligofructose by bacteria reduced this secretion of IL-1β. Whole-microbe intestinal washes from severe IBD patients were unable to ferment oligofructose or reduce fiber-associated inflammation in macrophage cells compared to remission or non-IBD children. Statistical analysis of food frequency questionnaire (FFQ) data on fiber consumption demonstrated that fiber-associated inflammation in patient biopsies cultured ex vivo (ELISA and qPCR) correlated with fiber avoidance (FFQ). Conclusions Comparing in vitro findings to our patient FFQs, intestinal washes (microbe abundance), and detailed patient history will better define the relationship between microbes, dietary fibers, and gut inflammation in IBD. This will allow for tailored dietary intervention through dietary recommendations, prebiotic, and/or probiotic therapies. Funding Agencies CCCWeston Foundation, WCHRI

Download Full-text

The effects of Malassezia on pro-inflammatory cytokine production by human peripheral blood mononuclear cells in vitro

Medical Mycology ◽

10.1046/j.1365-280x.1998.00137.x ◽

1998 ◽

Vol 36 (2) ◽

pp. 97-106 ◽

Cited By ~ 6

Author(s):

S. KESAVAN ◽

C. E. WALTERS ◽

K. T. HOLLAND ◽

E. INGHAM

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Inflammatory Cytokine ◽

Mononuclear Cells ◽

Cytokine Production ◽

Human Peripheral Blood ◽

Peripheral Blood Mononuclear ◽

Inflammatory Cytokine Production ◽

Blood Mononuclear Cells

Download Full-text

Oxidative Stress Compromises Lymphocyte Function in Neonatal Dairy Calves

Antioxidants ◽

10.3390/antiox10020255 ◽

2021 ◽

Vol 10 (2) ◽

pp. 255

Author(s):

Wilmer Cuervo ◽

Lorraine M. Sordillo ◽

Angel Abuelo

Keyword(s):

Oxidative Stress ◽

Immune Responses ◽

Immune Cell ◽

Lymphocyte Activation ◽

Dairy Calves ◽

Lymphocyte Function ◽

Newborn Calves ◽

Ifn Γ ◽

The Impact

Dairy calves are unable to mount an effective immune response during their first weeks of life, which contributes to increased disease susceptibility during this period. Oxidative stress (OS) diminishes the immune cell capabilities of humans and adult cows, and dairy calves also experience OS during their first month of life. However, the impact that OS may have on neonatal calf immunity remains unexplored. Thus, we aimed to evaluate the impact of OS on newborn calf lymphocyte functions. For this, we conducted two experiments. First, we assessed the association of OS status throughout the first month of age and the circulating concentrations of the cytokines interferon-gamma (IFN-γ) and interleukin (IL) 4, as well as the expression of cytokine-encoding genes IFNG, IL2, IL4, and IL10 in peripheral mononuclear blood cells (PBMCs) of 12 calves. Subsequently, we isolated PBMCs from another 6 neonatal calves to investigate in vitro the effect of OS on immune responses in terms of activation of lymphocytes, cytokine expression, and antibody production following stimulation with phorbol 12-myristate 13-acetate or bovine herpesvirus-1. The results were compared statistically through mixed models. Calves exposed to high OS status in their first month of age showed higher concentrations of IL-4 and expression of IL4 and IL10 and lower concentrations of IFN-γ and expression of IFNG and IL2 than calves exposed to lower OS. In vitro, OS reduced lymphocyte activation, production of antibodies, and protein and gene expression of key cytokines. Collectively, our results demonstrate that OS can compromise some immune responses of newborn calves. Hence, further studies are needed to explore the mechanisms of how OS affects the different lymphocyte subsets and the potential of ameliorating OS in newborn calves as a strategy to augment the functional capacity of calf immune cells, as well as enhance calves’ resistance to infections.

Download Full-text

A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections

International Journal of Molecular Sciences ◽

10.3390/ijms22031118 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1118

Author(s):

Abdulaziz Alamri ◽

Derek Fisk ◽

Deepak Upreti ◽

Sam K. P. Kung

Keyword(s):

Dendritic Cells ◽

Severe Acute Respiratory Syndrome ◽

Immune Responses ◽

Immune Cell ◽

Inflammatory Responses ◽

Viral Disease ◽

Cell Recruitment ◽

Cross Presentation ◽

Cell Immunity ◽

Immune Cell Recruitment

Dendritic cells (DC) connect the innate and adaptive arms of the immune system and carry out numerous roles that are significant in the context of viral disease. Their functions include the control of inflammatory responses, the promotion of tolerance, cross-presentation, immune cell recruitment and the production of antiviral cytokines. Based primarily on the available literature that characterizes the behaviour of many DC subsets during Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19), we speculated possible mechanisms through which DC could contribute to COVID-19 immune responses, such as dissemination of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to lymph nodes, mounting dysfunctional inteferon responses and T cell immunity in patients. We highlighted gaps of knowledge in our understanding of DC in COVID-19 pathogenesis and discussed current pre-clinical development of therapies for COVID-19.

Download Full-text

Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses

Scientific Reports ◽

10.1038/s41598-020-79068-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ricardo Louzada da Silva ◽

Diana M. Elizondo ◽

Nailah Z. D. Brandy ◽

Naomi L. Haddock ◽

Thomas A. Boddie ◽

...

Keyword(s):

Immune Evasion ◽

Inflammatory Cytokine ◽

Leishmania Donovani ◽

Cytokine Production ◽

Inflammatory Responses ◽

Bone Marrow Cells ◽

Parasitic Infections ◽

Inflammatory Factor ◽

Immune Functions ◽

Inflammatory Cytokine Production

AbstractMacrophages and monocytes are important for clearance of Leishmania infections. However, immune evasion tactics employed by the parasite results in suppressed inflammatory responses, marked by deficient macrophage functions and increased accumulation of monocytes. This results in an ineffective ability to clear parasite loads. Allograft Inflammatory Factor-1 (AIF1) is expressed in myeloid cells and serves to promote immune responses. However, AIF1 involvement in monocyte and macrophage functions during parasitic infections has not been explored. This study now shows that Leishmania donovani inhibits AIF1 expression in macrophages to block pro-inflammatory responses. Mice challenged with the parasite had markedly reduced AIF1 expression in splenic macrophages. Follow-up studies using in vitro approaches confirmed that L. donovani infection in macrophages suppresses AIF1 expression, which correlated with reduction in pro-inflammatory cytokine production and increased parasite load. Ectopic overexpression of AIF1 in macrophages provided protection from infection, marked by robust pro-inflammatory cytokine production and efficient pathogen clearance. Further investigations found that inhibiting AIF1 expression in bone marrow cells or monocytes impaired differentiation into functional macrophages. Collectively, results show that AIF1 is a critical regulatory component governing monocyte and macrophage immune functions and that L. donovani infection can suppress the gene as an immune evasion tactic.

Download Full-text