The prevalence of allergic diseases and asthma is increasing worldwide and according to the Global Initiative for Asthma (GINA), it is estimated there are approximately 260 million asthmatics in the world [1]. In Latin America, countries such as Brazil and Costa Rica have displayed similar prevalences in comparison with industrialized countries such as the United Kingdom and Australia [[2], [3], [4], [5]]. Such changes in developing countries may be explained by the hygiene hypothesis, which states that the increasing prevalence of allergic diseases is a result of reduced microbial exposure in early childhood, industrialization, improvement of health and hygiene conditions, indiscriminate use of antibiotics and access to vaccination [6].

The pathogenic mechanisms of allergic diseases are highly complex and have a strong association between genetic background and environmental factors [7,8]. For instance, atopic asthma is characterized by IgE-dependent mechanisms, an imbalance in driving the immune response, with bias for Th2 profile and the presence of inflammation with a predominance of eosinophils, mast cells and basophils [9,10]. Many studies have found associations between atopic asthma and environmental and genetic factors, mainly in developed countries [11,12]. In developing countries, on the other hand, non-atopic asthma has been, in some cases, more prevalent, suggesting the presence of different mechanisms, with Th2 and Th17-mixed profile, or absence of Th2 responses, or the predominance of neutrophilic inflammation [13,14]. In addition to these complex and different responses, several studies have also demonstrated a key role of the innate components, linking asthma not only to the endothelial and epithelial cells, but with the activity of the iNKTs cells and innate lymphoid cells (ILCs) [15,16].

Other important constituents of the innate immune system are the toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns (PAMPs). TLRs fundamental importance in the emergence of atopy and asthma is related to genetic variations in themselves and in the barriers of organisms [17]. In fact, different Toll-like Receptors (TLRs) modulate specific immune pathways. For instance, TLR2/1 and TLR2/6 heterodimers can shift the immune response towards a Th1 profile, thereby suppressing hallmark features of asthma such as eosinophilia and Th2 cytokine production [18]. The response triggered by TLR4 is dose-dependent; exposure to low doses of its agonist LPS can promote a Th2 response, while high doses elicits a Th1 profile [19,20].

TLR3, 7, 8, and 9 are primarily involved in antiviral defense. Notably, TLR9 activation has a protective role by promoting both Th1 and regulatory T-cell (Treg) responses. Conversely, the activation of TLR2 and TLR4 on mast cells can induce the release of pro-inflammatory mediators, exacerbating the disease [21]. Furthermore, polymorphisms in the TLR2 subfamily (TLR1, TLR6, TLR10) and in TLRs 3, 4, 7, 8, and 9 have been linked to an altered risk of developing asthma, atopy, and other allergic diseases [22]. These genetic variants can modify receptor expression or function, leading to an imbalance in the Th1/Th2 equilibrium, which in turn predisposes individuals to an exaggerated allergic immune response [23].

Although many studies have linked the presence of polymorphisms in the TLR genes as a risk factor for atopy and asthma [24], data regarding Latin America are still scarce, although it is in a transitional state as a region with a high prevalence of asthma and, different from developed countries also with a high prevalence of infections that could modulate immune response through TLRs interactions [25]. Thus, this study aimed to investigate the association between polymorphisms in the TLR genes, atopy and asthma in an urban Latin American population from Brazil.