High expression of Toll-like receptors 2 and 9 and Th1/Th2 cytokines profile in obese asthmatic children

Abstract

Asthma is a common pulmonary disease with chronic inflammation of the airways, and obesity is a chronic state of low-grade inflammation. Toll-like receptors (TLRs) are involved in the innate immune response. This study was designed to analyze whether obesity has an effect on the immune response of patients with asthma. We included obese asthmatic, obese, asthmatic, and healthy children. Biochemical and anthropometric analyses were performed. Interleukin (IL)-2, interferon (IFN) gamma, IL-4, IL-10, IL-1beta, and tumor necrosis factor alpha were measured. Peripheral blood mononuclear cells were analyzed by immunostaining with anti-TLR2 and anti-TLR9 antibodies. The data were expressed as means ± SEM or medians and percentiles. Kruskal-Wallis test and Dunn's multiple comparison test were applied. Asthmatic patients, both obese and nonobese, exhibited a mild asthma phenotype; none had infectious process, exacerbation, or acute symptoms during the 30 days before the inclusion in the study. The IL-2 and IFN-gamma levels in the obese asthmatic group were lower than in the other three groups. IL-4 levels in the obese asthmatic group were almost equal to those of the asthmatic group and more than in the other two groups, without significant difference. There were higher levels of TLR2 and TLR9 in obese asthmatic patients than in the other three groups. There is a decrease in Th1 cytokines in obese asthmatic patients, and we only found a trend to an increased Th2 profile. Patients studied do not appear to fit into any of the endotypes described until now. This is the first study showing the high expression of TLR2 and TLR9 in obese asthmatic patients. It is necessary to study other cytokines in obese asthmatic patients to see if it is possible to fit them into any of the already described endotypes or if it is a distinct endotype.

JNK–TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis

“…Synthetic TLR9 ligands (CpG ODNs) are shown to be beneficial in various animal models of asthma and even in a number of early human clinical trials , while CpG ODNs are also reported to activate TLR9 and cause lung inflammation . In fact, consistent with our previous report and the study of Carmen Maldonado‐Berna that high expression of TLR9 is found in asthma , the present study demonstrated that pronounced elevated expression of TLR9 was accompanying with lung inflammation exacerbation in WT mice after OVA challenges. However, such OVA‐induced inflammation including inflammatory cells around bronchial, mucus production in the airways, IgE level in the plasma, total and differential inflammatory cell infiltration in the BALF, and pro‐inflammatory cytokine production such as IL‐4 and IL‐13 was significantly attenuated in OVA‐challenged TLR9 −/− mice.…”

Vitamins C, E, and NADH on <i>in Vitro</i> Lymphocyte Proliferation and Redox Status among Obese Patients

“…However, IL-4 and IFNγ production by T lymphocytes after mitogen stimulation was reduced in obese patients compared with controls. Our findings were in agreement with a previous study that showed a decrease in cytokine secretion in obese patients [47] [48]. The INFγ/IL-4 ratio was unchanged in obese patients, reflecting no change in the profile of Th1/Th2 lymphocytes.…”

SP600125 promotes resolution of allergic airway inflammation via TLR9 in an OVA-induced murine acute asthma model

“…Several studies have suggested a mechanistic correlation between JNK signaling pathway and TLR9 (Tsai et al, 2012;Holley et al, 2012;Mitchell and Olive, 2010), and the levels of TLR9 are indeed higher in obese asthmatic patients (Sanchez-Zauco et al, 2014). TLRs are abundant on various innate immune cells involved in asthma pathogenesis, including eosinophils, mast cells, plasmacytoid DCs and epithelial cells (Sanchez-Zauco et al, 2014). When pathogens or allergens entering the airway, they may be recognized by the expressed TLRs of these cells, which triggers the activation of TLRs downstream signaling to induce defense action via initiating cytokines secretion (Lin et al, 2010).…”