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An introduction of the role of probiotics in human infections and autoimmune diseases
(2019) Campos, Helioswilton Sales de; Soares, Siomar de Castro; Oliveira, Carlo José Freire de
During the last decades, studies exploring the role of microorganisms inhabiting human body in different scenarios have demonstrated the great potential of modulating them to treat and prevent diseases. Among the most outstanding applications, probiotics have been used for over a century to treat infections and inflammation. Despite the beneficial role of other probiotics, Lactobacillus and Bifidobacterium species are the most frequently used, and have been effective as a therapeutic option in the treatment/prevention of dental caries, periodontal diseases, urogenital infections, and gastrointestinal infections. Additionally, as gastrointestinal tract harbors a great diversity of microbial species that directly or indirectly modulate host metabolism and immune response, the influence of intestinal microbiota, one of the targets of therapies using probiotics, on the biology of immune cells can be explored to treat inflammatory disorders or immune-mediated diseases. Thus, it is not surprising that probiotics have presented promising results in modulating human inflammatory diseases such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease, among others. Hence, the purpose of this review is to discuss the potential of therapeutic approaches using probiotics to constrain infection and development of inflammation on human subjects.
Pulmonary surfactant phosphatidylcholines induce immunological adaptation of alveolar macrophages
(2020) Loureiro, Luma da Costa; Gabriel Junior, Edson Alves; Roberto, Fabiana Albani Zambuzi; Fontanari, Caroline; Campos, Helioswilton Sales de; Frantz, Fabiani Gai; Faccioli, Lúcia Helena; Sorgi, Carlos Arterio
Pulmonary surfactant plays an important role in lung surface tension, defense against invading pathogens, and immune response. Furthermore, alveolar macrophages (AM) that comprise the front line of immune defense against inhaled microorganisms are covered by a layer of pulmonary fluid. Phosphatidylcholines (PCs), including unsaturated lipids such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), are the most prevalent phospholipids in pulmonary surfactant. POPC reacts with ozone to produce 1-palmitoyl-2-(9-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PONPC), a soluble mediator that initiates an inflammatory reaction in the lungs. However, the modulatory effects of POPC and PONPC on biology and activity of AM remain inconclusive. The exposure of AM (cell line AMJ2-C11) to POPC and PONPC was not directly related to the production of inflammatory mediators. However, AM, pre-incubated with POPC or PONPC, showed enhanced response after lipopolysaccharide (LPS) stimulation, and increased the production of nitric oxide and cytokines. This phenomenon was also observed for classical-polarized macrophages (M1). This increment on the production of inflammatory mediators was not associated with macrophage polarization, but with up-regulation of Tlr4 and Myd88 gene expression, which was in accordance with the adaptation of immune cells. This observation was confirmed by the histone acetylation epigenetic pathway. In contrast to the priming effect of POPC on AM activity, a harmful immune response, induced on incubation with PONPC, improved prostaglandin E2 (PGE2) formation, resulting in diminished bacterial phagocytosis. Additionally, PONPC induced production of CXCL1/KC, which potentially mediates neutrophil recruitment and enhances tissue inflammation. These results disclosed another dynamic mechanism by which pulmonary surfactant lipids (natural or oxidized) primed macrophage activity, thus affecting lung host defense.
An immunoinformatics-based designed multi-epitope candidate vaccine (mpme-VAC/STV-1) against Mycoplasma pneumoniae
(2022) Rodrigues, Thaís Cristina Vilela; Jaiswal, Arun Kumar; Lemes, Marcela Rezende; Silva, Marcos Vinícius da; Campos, Helioswilton Sales de; Alcantara, Luiz Carlos Júnior; Tosta, Stephane Fraga de Oliveira; Kato, Rodrigo Bentes; Alzahrani, Khalid J.
Pneumonia is a serious global health problem that accounts for over one million deaths annually. Among the main microorganisms causing pneumonia, Mycoplasma pneumoniae is one of the most common ones for which a vaccine is immediately required. In this context, a multi-epitope vaccine against this pathogen could be the best option that can induce effective immune response avoiding any serious adverse reactions. In this study, using an immunoinformatics approach we have designed a multi-epitope vaccine (mpme-VAC/STV-1) against M. pneumoniae. Our designed mpme-VAC/STV-1 is constructed using CTL (cytotoxic T lymphocyte), HTL (Helper T lymphocyte), and B-cell epitopes. These epitopes are selected from the core proteins of 88 M. pneumoniae genomes that were previously identified through reverse vaccinology approaches. The epitopes were filtered according to their immunogenicity, population coverage, and several other criteria. Sixteen CTL/B- and thirteen HTL/B- epitopes that belong to 5 core proteins were combined together through peptide linkers to develop the mpme-VAC/STV-1. The heat-labile enterotoxin from E. coli was used as an adjuvant. The designed mpme-VAC/STV-1 is predicted to be stable, non-toxic, non-allergenic, non-host homologous, and with required antigenic and immunogenic properties. Docking and molecular dynamic simulation of mpme-VAC/STV-1 shows that it can stimulate TLR2 pathway mediated immunogenic reactions. In silico cloning of mpme-VAC/STV-1 in an expression vector also shows positive results. Finally, the mpme-VAC/STV-1 also shows promising efficacy in immune simulation tests. Therefore, our constructed mpme-VAC/STV-1 could be a safe and effective multi-epitope vaccine for immunization against pneumonia. However, it requires further experimental and clinical validations.
Microbial-based therapies in the treatment of inflammatory bowel disease - an overview of human studies
(2019) Basso, Paulo José; Câmara, Niels Olsen Saraiva; Campos, Helioswilton Sales de
Inflammatory bowel disease (IBD) is a group of multifactorial and inflammatory infirmities comprised of two main entities: Ulcerative colitis (UC) and Crohn’s disease (CD). Classic strategies to treat IBD are focused on decreasing inflammation besides inducing and extending disease remission. However, these approaches have several limitations such as low responsiveness, excessive immunosuppression, and refractoriness. Despite the multifactorial causality of IBD, immune disturbances and intestinal dysbiosis have been suggested as the central players in disease pathogenesis. Hence, therapies aiming at modulating intestinal microbial composition may represent a promising strategy in IBD control. Fecal microbiota transplantation (FMT) and probiotics have been explored as promising candidates to reestablish microbial balance in several immune-mediated diseases such as IBD. These microbial-based therapies have demonstrated the ability to reduce both the dysbiotic environment and production of inflammatory mediators, thus inducing remission, especially in UC. Despite these promising results, there is still no consensus on the relevance of such treatments in IBD as a potential clinical strategy. Thus, this review aims to critically review and describe the use of FMT and probiotics to treat patients with IBD.
Absence of NOD2 receptor predisposes to intestinal inflammation by a deregulation in the immune response in hosts that are unable to control gut dysbiosis
(2018) Garcia, Patrícia Reis de Souza; Guimarães, Francielle Rodrigues; Campos, Helioswilton Sales de; Bonfá, Giuliano; Takahashi, Viviani Nardini; Lazo Chica, Javier Emilio; Turato, Walter Miguel; Silva, João Santana; Zamboni, Dario Simões; Cardoso, Cristina Ribeiro de Barros
Mutations in NOD2 predisposes to Inflammatory Bowel Diseases. Therefore, we evaluated the role of this innate receptor in the modulation of immunity in face of host microbiota changes. NOD2−/− mice presented higher susceptibility to experimental colitis than WT, with increased CD4 and CD8 T lymphocytes in the spleen. NOD2 deficiency also led to reduced Th17-related cytokines in the colon, with overall augmented IFN-γ in the gut and spleen. Nonetheless, there was increased frequency of CD4+IL-4+ cells in the mesenteric lymph nodes besides elevated CTLA-4 and FoxP3 regulatory markers in the spleen of NOD2-/- mice, although it did not result in more efficient control of gut inflammation. Indeed, these animals also had augmented IL-1β and IL-5 in the peritoneum, indicating that this receptor may be important to control bacteria translocation too. Microbiota exchanging between cohoused WT and NOD2−/− mice led to colitis worsening in the absence of the receptor, while antibiotic therapy in WT mice abrogated this effect. Then, not only the genetic mutation confers increased susceptibility to inflammation, but it is also influenced by the microbiota harbored by the host. Finally, NOD2-/- mice are more prone to intestinal inflammation due to deregulated immune response and increased susceptibility to colitogenic bacteria.