Pulmonary mucosal immunity mediated through CpG provides adequate protection against pulmonary Mycobacterium tuberculosis infection in the mouse model. A role for type I interferon

Troy, Amber; Esparza‐González, Sandra Cecilia; Bartek, Alicia; Creissen, Elizabeth; Izzo, Linda; Izzo, Angelo A.

doi:10.1016/j.tube.2020.101949

Cited by 12 publications

(8 citation statements)

References 62 publications

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“…Indeed, mucosal vaccines are able to induce both local and systemic immunity against infectious agents (93)(94)(95). Of interest, the addition (or codelivery) of potent adjuvants such as TLR-9 agonists has been described as efficient in potentiating a mucosal vaccination against mycobacterial infections (96).…”

Section: Discussionmentioning

confidence: 99%

TLR-9 Plays a Role in Mycobacterium leprae-Induced Innate Immune Activation of A549 Alveolar Epithelial Cells

Dias

Silva

et al. 2021

Front. Immunol.

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The respiratory tract is considered the main port of entry of Mycobacterium leprae, the causative agent of leprosy. However, the great majority of individuals exposed to the leprosy bacillus will never manifest the disease due to their capacity to develop protective immunity. Besides acting as a physical barrier, airway epithelium cells are recognized as key players by initiating a local innate immune response that orchestrates subsequent adaptive immunity to control airborne infections. However, to date, studies exploring the interaction of M. leprae with the respiratory epithelium have been scarce. In this work, the capacity of M. leprae to immune activate human alveolar epithelial cells was investigated, demonstrating that M. leprae-infected A549 cells secrete significantly increased IL-8 that is dependent on NF-κB activation. M. leprae was also able to induce IL-8 production in human primary nasal epithelial cells. M. leprae-treated A549 cells also showed higher expression levels of human β-defensin-2 (hβD-2), MCP-1, MHC-II and the co-stimulatory molecule CD80. Furthermore, the TLR-9 antagonist inhibited both the secretion of IL-8 and NF-κB activation in response to M. leprae, indicating that bacterial DNA sensing by this Toll-like receptor constitutes an important innate immune pathway activated by the pathogen. Finally, evidence is presented suggesting that extracellular DNA molecules anchored to Hlp, a histone-like protein present on the M. leprae surface, constitute major TLR-9 ligands triggering this pathway. The ability of M. leprae to immune activate respiratory epithelial cells herein demonstrated may represent a very early event during infection that could possibly be essential to the generation of a protective response.

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Section: Discussionmentioning

confidence: 99%

TLR-9 Plays a Role in Mycobacterium leprae-Induced Innate Immune Activation of A549 Alveolar Epithelial Cells

Dias

Silva

et al. 2021

Front. Immunol.

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“…In a recent report, it has been shown that CpG motifs can be used alone as a TLR9 adjuvant to elicit T-cell response in the mucosa [ 25 ]. In this in vivo study in mice, the authors showed that CpG type C, formulated in a liposome in combination with the antigen ESAT-6 and administrated intranasally, was able to reduce significantly the bacterial burden in the lung and that this adjutancy was probably due to type I IFN response by the activation of IFN-α and dendritic cell (DC) activation alongside a IFN-γ Th1 mechanism [ 25 ]. This study, along with others cited by the authors, makes an interesting contribution regarding immune responses to TB and vaccine candidates.…”

Section: Adjuvants In New Tb Vaccine Candidatesmentioning

confidence: 99%

“…This study, along with others cited by the authors, makes an interesting contribution regarding immune responses to TB and vaccine candidates. While the type I IFN response, during a natural infection with Mtb, is often associated with an exacerbation of the disease, in this case, the response was protection [ 25 ]. The hypothesis is that, when this pathway is acutely stimulated by a vaccine candidate, it induces a proinflammatory route but when the stimulation is chronical, during active TB disease, the type I IFN has a immunosuppressive effect [ 25 ].…”

Section: Adjuvants In New Tb Vaccine Candidatesmentioning

confidence: 99%

Developing New Anti-Tuberculosis Vaccines: Focus on Adjuvants

Franco

Peri

2021

Cells

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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that sits in the top 10 leading causes of death in the world today and is the current leading cause of death among infectious diseases. Although there is a licensed vaccine against TB, the Mycobacterium bovis bacilli Calmette–Guérin (BCG) vaccine, it has several limitations, namely its high variability of efficacy in the population and low protection against pulmonary tuberculosis. New vaccines for TB are needed. The World Health Organization (WHO) considers the development and implementation of new TB vaccines to be a priority. Subunit vaccines are promising candidates since they can overcome safety concerns and optimize antigen targeting. Nevertheless, these vaccines need adjuvants in their formulation in order to increase immunogenicity, decrease the needed antigen dose, ensure a targeted delivery and optimize the antigens delivery and interaction with the immune cells. This review aims to focus on adjuvants being used in new formulations of TB vaccines, namely candidates already in clinical trials and others in preclinical development. Although no correlates of protection are defined, most research lines in the field of TB vaccination focus on T-helper 1 (Th1) type of response, namely polyfunctional CD4+ cells expressing simultaneously IFN-γ, TNF-α, and IL-2 cytokines, and also Th17 responses. Accordingly, most of the adjuvants reviewed here are able to promote such responses. In the future, it might be advantageous to consider a wider array of immune parameters to better understand the role of adjuvants in TB immunity and establish correlates of protection.

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“…Additionally, the ability to use knockout and transgenic mice provides an additional level of interrogation for vaccine formulations and a better understanding of mechanisms involved in inducing protective immune responses ( 37 ). For instance, a recent analysis of the effect of intranasal vaccination using ODN as a molecular adjuvant showed that immunity could be achieved in a type I interferon-dependent manner ( 170 ). Another study demonstrated that intranasal vaccination was the best route for inducing protective immunity compared to intraperitoneal, subcutaneous, or intragastric routes ( 170 ).…”

Section: Animal Modelsmentioning

confidence: 99%

“…For instance, a recent analysis of the effect of intranasal vaccination using ODN as a molecular adjuvant showed that immunity could be achieved in a type I interferon-dependent manner ( 170 ). Another study demonstrated that intranasal vaccination was the best route for inducing protective immunity compared to intraperitoneal, subcutaneous, or intragastric routes ( 170 ). The cost of mouse models also allows for long-term immune profiling in vaccination studies.…”

Section: Animal Modelsmentioning

confidence: 99%

Advancing Adjuvants for Mycobacterium tuberculosis Therapeutics

et al. 2021

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Tuberculosis (TB) remains one of the leading causes of death worldwide due to a single infectious disease agent. BCG, the only licensed vaccine against TB, offers limited protection against pulmonary disease in children and adults. TB vaccine research has recently been reinvigorated by new data suggesting alternative administration of BCG induces protection and a subunit/adjuvant vaccine that provides close to 50% protection. These results demonstrate the need for generating adjuvants in order to develop the next generation of TB vaccines. However, development of TB-targeted adjuvants is lacking. To help meet this need, NIAID convened a workshop in 2020 titled “Advancing Vaccine Adjuvants for Mycobacterium tuberculosis Therapeutics”. In this review, we present the four areas identified in the workshop as necessary for advancing TB adjuvants: 1) correlates of protective immunity, 2) targeting specific immune cells, 3) immune evasion mechanisms, and 4) animal models. We will discuss each of these four areas in detail and summarize what is known and what we can advance on in order to help develop more efficacious TB vaccines.

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Pulmonary mucosal immunity mediated through CpG provides adequate protection against pulmonary Mycobacterium tuberculosis infection in the mouse model. A role for type I interferon

Cited by 12 publications

References 62 publications

TLR-9 Plays a Role in Mycobacterium leprae-Induced Innate Immune Activation of A549 Alveolar Epithelial Cells

TLR-9 Plays a Role in Mycobacterium leprae-Induced Innate Immune Activation of A549 Alveolar Epithelial Cells

Developing New Anti-Tuberculosis Vaccines: Focus on Adjuvants

Advancing Adjuvants for Mycobacterium tuberculosis Therapeutics

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