Promising Immunomodulatory Effects of Bacterial Lysates in Allergic Diseases

Abstract

In light of an escalating prevalence of allergic disorders, it is crucial to fully comprehend their pathophysiology and etiology. Such knowledge would play a pivotal role in the search for new therapeutic approaches concerning not only diseases’ symptoms, but also their underlying causes. The hygiene hypothesis indicates a high correlation between limited exposure to pathogens in early childhood and the risk of developing allergic disorders. Bearing in mind the significance of respiratory and digestive systems’ mucous membrane’s first-line exposure to pathogens as well as its implications on the host’s immune response, a therapy targeted at aforesaid membranes could guarantee promising and extensive treatment outcomes. Recent years yielded valuable information about bacterial lysates (BLs) known for having immunomodulatory properties. They consist of antigen mixtures obtained through lysis of bacteria which are the most common etiologic agents of respiratory tract infections. They interact with dendritic cells located in the mucous membranes of the upper respiratory tract and the gastrointestinal tract by toll-like receptors. The dendritic cells present acquired antigens resulting in innate immune response development on the release of chemokines, both stimulating monocytes and NK cells maturation and promoting polymorphonuclear neutrophil migration. Moreover, they influence the adaptive immune system by stimulating an increase of specific antibodies against administered bacterial antigens. The significance of BLs includes not only an anti-inflammatory effect on local infections but also restoration of Th1/Th2 balance, as demonstrated mainly in animal models. They decrease Th2-related cytokine levels (IL-4, IL-13) and increase Th1-related cytokine levels (IFN-γ). The reestablishment of the balance of the immune response leads to lowering atopic reactions incidence which, in addition to reduced risk of inflammation, provides the alleviation and improvement of clinical manifestations of allergic disorders. In this review, we hereby describe mechanisms of BLs action, considering their significant immunomodulatory role in innate immunity. The correlation between local, innate, and adaptive immune responses and their impact on the clinical course of allergic disorders are discussed as well. To conclude our review, we present up-to-date literature regarding the outcomes of BLs implemented in atopic dermatitis, allergic rhinitis, and asthma prevention and treatment, especially in children.

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“…Interestingly, the immune response activated by bacterial lysates is almost similar to the natural immune response provoked by pathogens [19,20]. When pathogens come in contact with the mucosa, as the first manifestation of mucosal innate immunity, pattern recognition receptors (PRRs) such as toll like receptors (TLRs) expressed on the host dendritic cells (DCs), macrophages, monocytes, and mast cells recognize the pathogen assisted molecular patterns (PAMPs), which are conserved molecular structures of the pathogens.…”

“…Microbial lysates or extracts (mostly polyvalent containing extracts of multiple species) are the products of bacterial and fungal cell lysis (cell disruption). Bacterial lysates in particular have been studied over several decades and are being used as potent immunostimulators/ immunomodulators for enhancing both innate and adaptive immunity [16][17][18][19][20][21][22]. Bacterial lysates are generally prepared by chemical (mainly alkaline cell lysis) or mechanical (lysis by high pressure shear or in bead mills) methods and they demonstrate therapeutic and prophylactic effects in the treatment of upper and lower respiratory tract infections (RTI) in both adults and paediatric patients [17][18][19][20].…”

“…Bacterial lysates in particular have been studied over several decades and are being used as potent immunostimulators/ immunomodulators for enhancing both innate and adaptive immunity [16][17][18][19][20][21][22]. Bacterial lysates are generally prepared by chemical (mainly alkaline cell lysis) or mechanical (lysis by high pressure shear or in bead mills) methods and they demonstrate therapeutic and prophylactic effects in the treatment of upper and lower respiratory tract infections (RTI) in both adults and paediatric patients [17][18][19][20]. In addition to their predominant use in the treatment of respiratory tract disorders like asthma, COPD and rhinitis, bacterial lysates have shown encouraging results in the treatment of various diseases like diverticulitis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, urinary tract infections, periodontitis, relapse of tuberculosis and food allergy [16][17][18][19][20][21][22].…”

“…Bacterial lysates contain bacterial components like proteins, lipopolysaccharides, peptidoglycans, ribosomes and nucleic acids [17][18][19][20], where proteins are the major component [28]. Given the size and structural complexity, proteins are very potent [29] antigens and immunogens too (immunogens are antigens, which elicit immune response after binding with the receptors).…”

“…Most of the studies on bacterial lysates are limited to their prophylactic use [16-22, 25, 26], though they are quite effective in the management of acute episodes too [36,37]. Bacterial lysates strengthen both innate and adaptive immunity [16][17][18][19][20][21][22]. They promote broad-spectrum nonspecific innate immune response by activating the macrophages and DCs.…”