Towards efficient immunotherapy for bacterial infection

McCulloch, Timothy R.; Wells, Timothy J.; Souza-Fonseca-Guimarães, Fernando

doi:10.1016/j.tim.2021.05.005

Cited by 50 publications

(44 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Up to date, the international consensus of the available approaches for the prevention of RRTi in children is immunotherapy, while probiotic treatment has not been suggested yet because it is not clear which bacteria strain, dosage, and administration schedule can offer the best results ( 45 ). The perspective of “new-age” immunotherapy, such as checkpoint inhibition triggering the immunopathology events or cytokine therapies modulating inflammation development, has been raised to reduce the burden of infectious diseases threatened by antibiotic resistance ( 46 ). The recent meta-analysis has shown that the immunostimulants, OM-85 BV and pidotimod, which have been widely used and suggested by pediatricians in the prevention and treatment of RRTi in susceptible children, can reduce the incidence of respiratory tract infections by 0.21 and 0.19 per month, respectively ( 47 ); however, long-term use of the said drugs is challenging for children and their families.…”

Section: Discussionmentioning

confidence: 99%

Oropharyngeal Probiotic ENT-K12 as an Effective Dietary Intervention for Children With Recurrent Respiratory Tract Infections During Cold Season

et al. 2022

View full text Add to dashboard Cite

Recurrent respiratory tract infections (RRTi) cause a high burden of disease and lead to negative impact on quality of life, frequent school/work absenteeism, and doctor visits, which remain a great challenge to pediatricians because RRTi can increase the risk of various complications including antibiotic overuse and resistance, which is one of the biggest threats to global health, and there is no confirmed effective treatment. In this study, we aimed to assess the clinical efficacy and safety of oropharyngeal probiotic ENT-K12 as a dietary intervention or a complementary treatment along with standard medical treatment during acute respiratory infections among children with RRTi during cold season. The results of this study show that when comparing to practicing of standard medical treatment only, the complementary intake of oropharyngeal probiotic ENT-K12 can effectively reduce episodes of both acute and RRTi in school children, shorten the course of respiratory symptoms onset, reduce the use of antibiotics and antiviral drugs, and reduce the absence days from both children's school and parents' work. Using oropharyngeal probiotics as a complementary dietary intervention to stabilize oropharyngeal microflora, specifically inhibiting respiratory pathogens and enhancing host immunity, could possibly be a promising approach to reduce RRTi burden and combating antibiotic resistance in long term, more clinical studies will be needed to further confirm the clinical practicing guide to ensure its clinical benefit.MethodsA total of 100 susceptible children with RRTi aged 3–10 years, living in Wuhan, China, were selected. They were randomized to the probiotic group and control group at the beginning of the trial during the cold season. Fifty children in the probiotic group took oropharyngeal probiotic ENT-K12 for 30 days, along with standard medical treatment when there was an onset of respiratory symptoms and medical treatment was needed, and fifty children in the control group did not take oropharyngeal probiotics but only had standard medical treatment when there was an onset of respiratory symptoms and medical treatment was needed. Patients were followed up for 30 days during the cold season. The primary objective of this study is to assess the complementary dietary interventional efficacy of oropharyngeal probiotic ENT-K12 on episodes of respiratory tract infections during the cold season, and the secondary objective is to assess the interventional efficacy of oropharyngeal probiotic on days of respiratory symptoms onset, using antiviral drugs, antibiotics, and antipyretics, days of children absent from school, and days of parents absent from work, as well as to confirm tolerability and safety judged by adverse event reporting.ResultsThere were 47 children, 22 male and 25 female children, with an average age of 5.71 years (SD = 1.99) in the probiotic group finishing the study, and 50 children, 32 male and 18 female children, in the control group with an average age of 6.12 years (SD = 1.98) finishing the study. During the 30-day period of oropharyngeal probiotic intake, children in the probiotic group totally had 7 episodes of upper respiratory tract infections, while children in the control group totally had 17 episodes of upper respiratory tract infections, indicating that the incidence of upper respiratory tract infection in the probiotic group (14.89%) was significantly lower than that in the control group (34.00%) during the intervention period. The days of using antibiotics and antiviral drugs in the probiotic group were significantly lower than that in the control group, and the course of respiratory symptoms onset was shorter and more moderate in the probiotic group than that in the control group; in addition, compared with the control group, both the days of children absent from school and parents' absence from work in the probiotic group were significantly lower. Children treated with oropharyngeal probiotic ENT-K12 had excellent tolerability with no side effects reported, hence confirmed safety of applying oropharyngeal probiotic ENT-K12 as a prophylactic use or an effective dietary intervention along with standard medication during respiratory infections onset.ConclusionIntake of oropharyngeal probiotic ENT-K12 as a dietary intervention can effectively reduce episodes of upper respiratory tract infections in school children with RRTi during high peak season, reduce the days of using antibiotics and antiviral drugs, and reduce children's sick leave days, parents' absence days from work, and shorten the course of respiratory infections; the safety of oropharyngeal probiotic ENT-K12 has been confirmed with no side effects reported, excellent tolerability, and easy acceptance. Notably, this study opens up a new research idea in the field of microbe promoting human health by supplying direct proof to support its efficiency and safety.

show abstract

Section: Discussionmentioning

confidence: 99%

Oropharyngeal Probiotic ENT-K12 as an Effective Dietary Intervention for Children With Recurrent Respiratory Tract Infections During Cold Season

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Immune checkpoint inhibitors reversing the exhausted phenotype of T cells are another strategy ( 12 ). However, the role of well-described T cell immune checkpoints such as PD-1, CTLA-4, TIM-3, and B7-H3 in the control of NK cell tolerance is unclear and they seem to promote different effects than those described and expected for T cells ( 41 ). Nevertheless, TIM-3 was found to be expressed on NK cells, and anti-TIM-3 antibody in combination with a superagonist of IL-15 (ALT-803) enhanced NK cell cytotoxicity against osteosarcoma cells ex vivo ( 42 ).…”

Section: Tipping the Balance Toward Activationmentioning

confidence: 99%

Enhancing Natural Killer Cell Targeting of Pediatric Sarcoma

et al. 2021

Self Cite

View full text Add to dashboard Cite

Osteosarcoma, Ewing sarcoma (EWS), and rhabdomyosarcoma (RMS) are the most common pediatric sarcomas. Conventional therapy for these sarcomas comprises neoadjuvant and adjuvant chemotherapy, surgical resection of the primary tumor and/or radiation therapy. Patients with metastatic, relapsed, or refractory tumors have a dismal prognosis due to resistance to these conventional therapies. Therefore, innovative therapeutic interventions, such as immunotherapy, are urgently needed. Recently, cancer research has focused attention on natural killer (NK) cells due their innate ability to recognize and kill tumor cells. Osteosarcoma, EWS and RMS, are known to be sensitive to NK cell cytotoxicity in vitro. In the clinical setting however, NK cell cytotoxicity against sarcoma cells has been mainly studied in the context of allogeneic stem cell transplantation, where a rapid immune reconstitution of NK cells plays a key role in the control of the disease, known as graft-versus-tumor effect. In this review, we discuss the evidence for the current and future strategies to enhance the NK cell-versus-pediatric sarcoma effect, with a clinical focus. The different approaches encompass enhancing antibody-dependent NK cell cytotoxicity, counteracting the NK cell mechanisms of self-tolerance, and developing adoptive NK cell therapy including chimeric antigen receptor-expressing NK cells.

show abstract

“…Bacterial infections caused by opportunistic pathogens or invading pathogenic bacteria are the major infectious diseases worldwide, causing many diseases, including pneumonia, periodontitis, tuberculosis, conjunctivitis, gastroenteritis, and sepsis (1)(2)(3)(4)(5). Although antibiotics have enabled great success in preventing and treating bacterial infections, overconsumption and misuse have unfortunately increased the prevalence of mutidrug-resistant (MDR) microbes (6,7). A study that collected the total medical expenditure of inpatients in China from 2013 to 2015 reported an additional medical expenditure of US $15,557.25 per inpatient with a healthcare-associated infection (HAI) caused by antimicrobial resistance (AMR) infection compared with that without an HAI (8).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the resurgence of bacterial infections has made them a pressing public health concern once again. In this context, researchers are striving to develop new strategies to treat bacterial infections and avoid drug resistance, among which immunotherapy is an important research direction due to its breakthroughs and advantages in the treatment of cancer and autoimmune diseases ( 7 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

The cGAS-STING Pathway in Bacterial Infection and Bacterial Immunity

et al. 2022

View full text Add to dashboard Cite

Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS), along with the adaptor stimulator of interferon genes (STING), are crucial components of the innate immune system, and their study has become a research hotspot in recent years. Many biochemical and structural studies that have collectively elucidated the mechanism of activation of the cGAS-STING pathway with atomic resolution have provided insights into the roles of the cGAS-STING pathway in innate immunity and clues to the origin and evolution of the modern cGAS-STING signaling pathway. The cGAS-STING pathway has been identified to protect the host against viral infection. After detecting viral dsDNA, cGAS synthesizes a second messenger to activate STING, eliciting antiviral immune responses by promoting the expression of interferons (IFNs) and hundreds of IFN-stimulated genes (ISGs). Recently, the cGAS-STING pathway has also been found to be involved in response to bacterial infections, including bacterial pneumonia, melioidosis, tuberculosis, and sepsis. However, compared with its functions in viral infection, the cGAS-STING signaling pathway in bacterial infection is more complex and diverse since the protective and detrimental effects of type I IFN (IFN-I) on the host depend on the bacterial species and infection mode. Besides, STING activation can also affect infection prognosis through other mechanisms in different bacterial infections, independent of the IFN-I response. Interestingly, the core protein components of the mammalian cGAS-STING signaling pathway have been found in the bacterial defense system, suggesting that this widespread signaling pathway may have originated in bacteria. Here, we review recent findings related to the structures of major molecules involved in the cGAS-STING pathway and the effects of the cGAS-STING pathway in various bacterial infections and bacterial immunity, which may pave the way for the development of new antibacterial drugs that specifically kill bacteria without harmful effects on the host.

show abstract

Towards efficient immunotherapy for bacterial infection

Cited by 50 publications

References 95 publications

Oropharyngeal Probiotic ENT-K12 as an Effective Dietary Intervention for Children With Recurrent Respiratory Tract Infections During Cold Season

Oropharyngeal Probiotic ENT-K12 as an Effective Dietary Intervention for Children With Recurrent Respiratory Tract Infections During Cold Season

Enhancing Natural Killer Cell Targeting of Pediatric Sarcoma

The cGAS-STING Pathway in Bacterial Infection and Bacterial Immunity

Contact Info

Product

Resources

About