scholarly journals Mycobacterium tuberculosis PE_PGRS20 and PE_PGRS47 Proteins Inhibit Autophagy by Interaction with Rab1A

mSphere ◽  
2021 ◽  
Author(s):  
Emily J. Strong ◽  
Tony W. Ng ◽  
Steven A. Porcelli ◽  
Sunhee Lee
Keyword(s):  
Infectious Disease ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Cellular Process ◽  
Phagocytic Cells ◽  
Adaptive Immune Responses ◽  
Content Type ◽  
Adaptive Immune ◽  
Intracellular Infections

Tuberculosis is a significant global infectious disease caused by infection of the lungs with Mycobacterium tuberculosis , which then resides and replicates mainly within host phagocytic cells. Autophagy is a complex host cellular process that helps control intracellular infections and enhance innate and adaptive immune responses.

scholarly journals Acellular Pertussis Vaccines and Pertussis Resurgence: Revise or Replace?

mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Clara Maria Ausiello ◽  
Antonio Cassone
Keyword(s):  
Immune Responses ◽  
Whooping Cough ◽  
Experimental Models ◽  
Adaptive Immune Responses ◽  
Content Type ◽  
Antigenic Composition ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Antibody Levels ◽  
Stimulation Of

ABSTRACTThe resurgence of pertussis (whooping cough) in countries with high vaccination coverage is alarming and invites reconsideration of the use of current acellular pertussis (aP) vaccines, which have largely replaced the old, reactogenic, whole-cell pertussis (wP) vaccine. Some drawbacks of these vaccines in terms of limited antigenic composition and early waning of antibody levels could be anticipated by the results of in-trial or postlicensure human investigations of B- and T-cell responses in aP versus wP vaccine recipients or unvaccinated, infected children. Recent data in experimental models, including primates, suggest that generation of vaccines capable of a potent, though regulated, stimulation of innate immunity driving effective, persistent adaptive immune responses againstBordetella pertussisinfection should be privileged. Adjuvants that skew Th1/Th17 responses or new wP (detoxified or attenuated) vaccines should be explored. Nonetheless, the high merits of the current aP vaccines in persuading people to resume vaccination against pertussis should not be forgotten.

scholarly journals Lessons from Bacillus Calmette-Guérin: Harnessing Trained Immunity for Vaccine Development

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2109
Author(s):  
Samuel T. Pasco ◽  
Juan Anguita
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Vaccine Development ◽  
Vaccine Design ◽  
Innate Immune ◽  
Bacillus Calmette Guerin ◽  
Adaptive Immune Responses ◽  
Trained Immunity ◽  
Adaptive Immune ◽  
Potential Methods

Vaccine design traditionally focuses on inducing adaptive immune responses against a sole target pathogen. Considering that many microbes evade innate immune mechanisms to initiate infection, and in light of the discovery of epigenetically mediated innate immune training, the paradigm of vaccine design has the potential to change. The Bacillus Calmette-Guérin (BCG) vaccine induces some level of protection against Mycobacterium tuberculosis (Mtb) while stimulating trained immunity that correlates with lower mortality and increased protection against unrelated pathogens. This review will explore BCG-induced trained immunity, including the required pathways to establish this phenotype. Additionally, potential methods to improve or expand BCG trained immunity effects through alternative vaccine delivery and formulation methods will be discussed. Finally, advances in new anti-Mtb vaccines, other antimicrobial uses for BCG, and “innate memory-based vaccines” will be examined.

scholarly journals Epithelial Phosphatidylinositol-3-Kinase Signaling Is Required for β-Catenin Activation and Host Defense against Citrobacter rodentium Infection

2011 ◽  
Vol 79 (5) ◽  
pp. 1863-1872 ◽  
Author(s):  
Jeffrey B. Brown ◽  
Paul Cheresh ◽  
Tatiana Goretsky ◽  
Elizabeth Managlia ◽  
Gery R. Grimm ◽  
...  
Keyword(s):  
Immune Responses ◽  
Host Defense ◽  
Bacterial Clearance ◽  
Phosphatidylinositol 3 Kinase ◽  
Adaptive Immune Responses ◽  
Content Type ◽  
Akt Activation ◽  
Adaptive Immune ◽  
Pi3k Inhibition ◽  
Pi3k Activation

ABSTRACTCitrobacter rodentiuminfection of mice induces cell-mediated immune responses associated with crypt hyperplasia and epithelial β-catenin signaling. Recent data suggest that phosphatidylinositol-3-kinase (PI3K)/Akt signaling cooperates with Wnt to activate β-catenin in intestinal stem and progenitor cells through phosphorylation at Ser552 (P-β-catenin552). Our aim was to determine whether epithelial PI3K/Akt activation is required for β-catenin signaling and host defense againstC. rodentium. C57BL/6 mice were infected withC. rodentiumand treated with dimethyl sulfoxide (DMSO) (vehicle control) or with the PI3K inhibitor LY294002 or wortmannin. The effects of infection on PI3K activation and β-catenin signaling were analyzed by immunohistochemistry. The effects of PI3K inhibition on host defense were analyzed by the quantification of splenic and colon bacterial clearance, and adaptive immune responses were measured by real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Increased numbers of P-β-catenin552-stained epithelial cells were found throughout expanded crypts inC. rodentiumcolitis. We show that the inhibition of PI3K signaling attenuates epithelial Akt activation, the Ser552 phosphorylation and activation of β-catenin, and epithelial cell proliferative responses duringC. rodentiuminfection. PI3K inhibition impairs bacterial clearance despite having no impact on mucosal cytokine (gamma interferon [IFN-γ], tumor necrosis factor [TNF], interleukin-17 [IL-17], and IL-1β) or chemokine (CXCL1, CXCL5, CXCL9, and CXCL10) induction. The results suggest that the host defense againstC. rodentiumrequires epithelial PI3K activation to induce Akt-mediated β-catenin signaling and the clearance ofC. rodentiumindependent of adaptive immune responses.

scholarly journals Phagocytosed Polyhedrin-Cytokine Cocrystal Nanoparticles Provide Sustained Secretion of Bioactive Cytokines from Macrophages

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Astrid Wendler ◽  
Nicholas James ◽  
Michael H. Jones ◽  
Christian Pernstich
Keyword(s):  
Drug Delivery ◽  
Wound Healing ◽  
Immune Responses ◽  
Tissue Homeostasis ◽  
Potential Utility ◽  
Active Process ◽  
Phagocytic Cells ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Monocytes And Macrophages

Many cells possess the ability to engulf and incorporate particles by phagocytosis. This active process is characteristic of microorganisms as well as higher order species. In mammals, monocytes, macrophages, and microglia are among the so-called professional phagocytes. In addition, cells such as fibroblast and chondrocytes are classified as nonprofessional phagocytes. Professional phagocytes play important roles in both the innate and adaptive immune responses, wound healing, and tissue homeostasis. Consequently, these cells are increasingly studied as targets and vectors of therapeutic intervention to treat a range of diseases. Professional phagocytes are notoriously difficult to transfect limiting their study and manipulation. Consequently, efforts have shifted towards the development of nanoparticles to deliver a cargo to phagocytic cells via phagocytosis. However, this approach carries significant technical challenges, particularly for protein cargos. We have focused on the development of nanoscale cocrystalline protein depots, known as PODS®, that contain protein cargos, including cytokines. Here, we show that PODS are readily phagocytosed by nonprofessional as well as professional phagocytic cells and have attributes, such as highly sustained release of cargo, that suggest potential utility for the study and exploitation of phagocytic cells for drug delivery. Monocytes and macrophages that ingest PODS retain normal characteristics including a robust chemotactic response. Moreover, the PODS-cytokine cargo is secreted by the loaded cell at a level sufficient to modulate the behavior of surrounding nonphagocytic cells. The results presented here demonstrate the potential of PODS nanoparticles as a novel molecular tool for the study and manipulation of phagocytic cells and for the development of Trojan horse immunotherapy strategies to treat cancer and other diseases.

scholarly journals MyD88 Signaling Is Required for Efficient Innate and Adaptive Immune Responses to Paracoccidioides brasiliensis Infection

2011 ◽  
Vol 79 (6) ◽  
pp. 2470-2480 ◽  
Author(s):  
Flávio V. Loures ◽  
Adriana Pina ◽  
Maíra Felonato ◽  
Claudia Feriotti ◽  
Eliseu F. de Araújo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Paracoccidioides Brasiliensis ◽  
Fungal Growth ◽  
Yeast Cells ◽  
Adaptive Immune Responses ◽  
Content Type ◽  
Adaptive Immune ◽  
Initial Interaction ◽  
Low Levels ◽  
Myd88 Signaling

ABSTRACTThe mechanisms that govern the initial interaction betweenParacoccidioides brasiliensis, a primary dimorphic fungal pathogen, and cells of the innate immunity need to be clarified. Our previous studies showed that Toll-like receptor 2 (TLR2) and TLR4 regulate the initial interaction of fungal cells with macrophages and the pattern of adaptive immunity that further develops. The aim of the present investigation was to assess the role of MyD88, an adaptor molecule used by TLRs to activate genes of the inflammatory response in pulmonary paracoccidioidomycosis. Studies were performed with normal and MyD88−/−C57BL/6 mice intratracheally infected withP. brasiliensisyeast cells. MyD88−/−macrophages displayed impaired interaction with fungal yeast cells and produced low levels of IL-12, MCP-1, and nitric oxide, thus allowing increased fungal growth. Compared with wild-type (WT) mice, MyD88−/−mice developed a more severe infection of the lungs and had marked dissemination of fungal cells to the liver and spleen. MyD88−/−mice presented low levels of Th1, Th2, and Th17 cytokines, suppressed lymphoproliferation, and impaired influx of inflammatory cells to the lungs, and this group of cells comprised lower numbers of neutrophils, activated macrophages, and T cells. Nonorganized, coalescent granulomas, which contained high numbers of fungal cells, characterized the severe lesions of MyD88−/−mice; the lesions replaced extensive areas of several organs. Therefore, MyD88−/−mice were unable to control fungal growth and showed a significantly decreased survival time. In conclusion, our findings demonstrate that MyD88 signaling is important in the activation of fungicidal mechanisms and the induction of protective innate and adaptive immune responses againstP. brasiliensis.

scholarly journals Exposure of Monocytes to Lipoarabinomannan Promotes Their Differentiation into Functionally and Phenotypically Immature Macrophages

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Leslie Chávez-Galán ◽  
Ranferi Ocaña-Guzmán ◽  
Luis Torre-Bouscoulet ◽  
Carolina García-de-Alba ◽  
Isabel Sada-Ovalle
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Etiologic Agent ◽  
Human Monocytes ◽  
Adaptive Immune Responses ◽  
Phagocytic Capacity ◽  
Monocyte Differentiation ◽  
Tuberculosis Patients ◽  
Adaptive Immune

Lipoarabinomannan (LAM) is a lipid virulence factor secreted byMycobacterium tuberculosis(Mtb), the etiologic agent of tuberculosis. LAM can be measured in the urine or serum of tuberculosis patients (TB-patients). Circulating monocytes are the precursor cells of alveolar macrophages and might be exposed to LAM in patients with active TB. We speculated that exposing monocytes to LAM could produce phenotypically and functionally immature macrophages. To test our hypothesis, human monocytes were stimulated with LAM (24–120 hours) and various readouts were measured. The study showed that when monocytes were exposed to LAM, the frequency of CD68+, CD33+, and CD86+macrophages decreased, suggesting that monocyte differentiation into mature macrophages was affected. Regarding functionality markers, TLR2+and TLR4+macrophages also decreased, but the percentage of MMR+expression did not change. LAM-exposed monocytes generated macrophages that were less efficient in producing proinflammatory cytokines such as TNF-αand IFN-γ; however, their phagocytic capacity was not modified. Taken together, these data indicate that LAM exposure influenced monocyte differentiation and produced poorly functional macrophages with a different phenotype. These results may help us understand how mycobacteria can limit the quality of the innate and adaptive immune responses.

scholarly journals Subunit Vaccine ESAT-6:c-di-AMP Delivered by Intranasal Route Elicits Immune Responses and Protects Against Mycobacterium tuberculosis Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Huanhuan Ning ◽  
Wei Zhang ◽  
Jian Kang ◽  
Tianbing Ding ◽  
Xuan Liang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Subunit Vaccine ◽  
Mucosal Vaccine ◽  
Intranasal Route ◽  
Mycobacterium Tuberculosis Infection ◽  
Adaptive Immune Responses ◽  
Common Cause ◽  
Adaptive Immune ◽  
A Subunit

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains the most common cause of death from a single infectious disease. More safe and effective vaccines are necessary for preventing the prevalence of TB. In this study, a subunit vaccine of ESAT-6 formulated with c-di-AMP (ESAT-6:c-di-AMP) promoted mucosal and systemic immune responses in spleen and lung. ESAT-6:c-di-AMP inhibited the differentiations of CD8+ T cells as well as macrophages, but promoted the differentiations of ILCs in lung. The co-stimulation also enhanced inflammatory cytokines production in MH-S cells. It was first revealed that ESAT-6 and c-di-AMP regulated autophagy of macrophages in different stages, which together resulted in the inhibition of Mtb growth in macrophages during early infection. After Mtb infection, the level of ESAT-6-specific immune responses induced by ESAT-6:c-di-AMP dropped sharply. Finally, inoculation of ESAT-6:c-di-AMP led to significant reduction of bacterial burdens in lungs and spleens of immunized mice. Our results demonstrated that subunit vaccine ESAT-6:c-di-AMP could elicit innate and adaptive immune responses which provided protection against Mtb challenge, and c-di-AMP as a mucosal adjuvant could enhance immunogenicity of antigen, especially for innate immunity, which might be used for new mucosal vaccine against TB.

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