Bet v 1 contiguous overlapping peptides anchored to virosomes with TLR4 agonist enhance immunotherapy efficacy in mice

Recent data argue for a pro-inflammatory role of CAMP (cathelicidin antimicrobial peptide) in adipocytes and adipose tissue (AT) and for regulatory circuits involving TLRs. In order to investigate regulatory effects of TLR2 and TLR4, 3T3-L1 adipocytes were stimulated with TLR2 agonistic lipopeptide MALP-2 and with TLR4 agonist LPS in presence or absence of signal transduction inhibitors. CAMP gene expression was analysed by quantitative real-time PCR in adipocytes and in murine AT compartments and cellular subfractions. CAMP expression was higher in gonadal than in subcutaneous AT and there was a gender-specific effect with higher levels in males. Adipocytes had higher CAMP expression than the stroma-vascular cell (SVC) fraction. MALP-2 up-regulated CAMP expression significantly, mediated by STAT3 and PI3K and potentially (non-significant trend) by NF-κB and MAPK, but not by raf-activated MEK-1/-2. Moreover, LPS proved to act as a potent inducer of CAMP via NF-κB, PI3K and STAT3, whereas specific inhibition of MAPK and MEK-1/-2 had no effect. In conclusion, activation of TLR2 and TLR4 by classical ligands up-regulates adipocyte CAMP expression involving classical signal transduction elements. These might represent future drug targets for pharmacological modulation of CAMP expression in adipocytes, especially in the context of metabolic and infectious diseases.

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Epicutaneous immune modulation with Bet v 1 plus R848 suppresses allergic asthma in a murine model

Allergy ◽

10.1111/all.12326 ◽

2013 ◽

Vol 69 (3) ◽

pp. 328-337 ◽

Cited By ~ 24

Author(s):

S. Siebeneicher ◽

S. Reuter ◽

M. Krause ◽

A. Wangorsch ◽

J. Maxeiner ◽

...

Keyword(s):

Allergic Asthma ◽

Murine Model ◽

Immune Modulation ◽

Bet V 1

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Adsorption of Toll-Like Receptor 4 Agonist to Alum-Based Tetanus Toxoid Vaccine Dampens Pro-T Helper 2 Activities and Enhances Antibody Responses

Journal of Immunology Research ◽

10.1155/2015/280238 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Juliana Bortolatto ◽

Luciana Mirotti ◽

Dunia Rodriguez ◽

Eliane Gomes ◽

Momtchilo Russo

Keyword(s):

Tetanus Toxoid ◽

Lipid A ◽

Antibody Responses ◽

Aluminum Salts ◽

T Helper 2 ◽

Monophosphoryl Lipid A ◽

Tlr4 Agonist ◽

Specific Antibody Production ◽

Humoral Responses

Aluminum salts gels (alum) are TLR-independent adjuvants and have been used to boost antibody responses in alum-based vaccines such as diphtheria, pertussis, and tetanus toxoid (DPT) triple vaccine. However, the pro-Th2 activity of alum-based vaccine formulations has not been fully appreciated. Here we found that alum-based tetanus toxoid (TT) vaccine was biased toward a Th-2 profile as shown by TT-induced airway eosinophilic inflammation, type 2 cytokine production, and high levels of IgE anaphylactic antibodies. The adsorption into alum of prototypic TLR4 agonists such as lipopolysaccharides (LPS) derived fromEscherichia coliconsistently dampened TT-induced Th2 activities without inducing IFNγor Th1-like responses in the lung. Conversely, adsorption of monophosphoryl lipid A (MPLA) extracted fromSalmonella minnesota, which is a TIR-domain-containing adapter-inducing interferon-β- (TRIF-) biased TLR4 agonist, was less effective in decreasing Th-2 responses. Importantly, in a situation with antigenic competition (OVA plus TT), TT-specific IgG1 or IgG2a was decreased compared with TT sensitization. Notably, LPS increased the production of IgG1 and IgG2a TT-specific antibodies. In conclusion, the addition of LPS induces a more robust IgG1 and IgG2a TT-specific antibody production and concomitantly decreases Th2-cellular and humoral responses, indicating a potential use of alum/TLR-based vaccines.

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