scholarly journals Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity

2006 ◽  
Vol 203 (2) ◽  
pp. 413-424 ◽  
Author(s):  
Troy Querec ◽  
Soumaya Bennouna ◽  
Sefik Alkan ◽  
Yasmina Laouar ◽  
Keith Gorden ◽  
...  
Keyword(s):  
Immune Responses ◽  
Yellow Fever ◽  
Yellow Fever Vaccine ◽  
Interferon Α ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Immunological Mechanisms ◽  
History Of ◽  
History Of Use ◽  
Deficient Mice

The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines available, with a 65-yr history of use in >400 million people globally. Despite this efficacy, there is presently no information about the immunological mechanisms by which YF-17D acts. Here, we present data that suggest that YF-17D activates multiple Toll-like receptors (TLRs) on dendritic cells (DCs) to elicit a broad spectrum of innate and adaptive immune responses. Specifically, YF-17D activates multiple DC subsets via TLRs 2, 7, 8, and 9 to elicit the proinflammatory cytokines interleukin (IL)-12p40, IL-6, and interferon-α. Interestingly, the resulting adaptive immune responses are characterized by a mixed T helper cell (Th)1/Th2 cytokine profile and antigen-specific CD8+ T cells. Furthermore, distinct TLRs appear to differentially control the Th1/Th2 balance; thus, whilst MyD88-deficient mice show a profound impairment of Th1 cytokines, TLR2-deficient mice show greatly enhanced Th1 and Tc1 responses to YF-17D. Together, these data enhance our understanding of the molecular mechanism of action of YF-17D, and highlight the potential of vaccination strategies that use combinations of different TLR ligands to stimulate polyvalent immune responses.

Characterization of main cytokine sources from the innate and adaptive immune responses following primary 17DD yellow fever vaccination in adults

Vaccine ◽  
2011 ◽  
Vol 29 (3) ◽  
pp. 583-592 ◽  
Author(s):  
Maria Luiza Silva ◽  
Marina Angela Martins ◽  
Luçandra Ramos Espírito-Santo ◽  
Ana Carolina Campi-Azevedo ◽  
Denise Silveira-Lemos ◽  
...  
Keyword(s):  
Immune Responses ◽  
Yellow Fever ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Yellow Fever Vaccination

scholarly journals Metal-induced delayed type hypersensitivity responses potentiate particle induced osteolysis in a sex and age dependent manner

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251885
Author(s):  
Lauryn Samelko ◽  
Marco Caicedo ◽  
Kyron McAllister ◽  
Joshua Jacobs ◽  
Nadim James Hallab
Keyword(s):  
Immune Responses ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Delayed Type Hypersensitivity ◽  
Adaptive Immune Responses ◽  
Male And Female ◽  
Female Mice ◽  
Adaptive Immune ◽  
Caspase 1 ◽  
Deficient Mice

It is widely recognized that innate macrophage immune reactions to implant debris are central to the inflammatory responses that drive biologic implant failure over the long term. Less common, adaptive lymphocyte immune reactions to implant debris, such as delayed type hypersensitivity (DTH), can also affect implant performance. It is unknown which key patient factors, if any, mediate these adaptive immune responses that potentiate particle/macrophage mediated osteolysis. The objective of this investigation was to determine to what degree known adaptive immune responses to metal implant debris can affect particle-induced osteolysis (PIO); and if this pathomechanism is dependent on: 1) innate immune danger signaling, i.e., NLRP3 inflammasome activity, 2) sex, and/or 3) age. We used an established murine calvaria model of PIO using male and female wild-type C57BL/6 vs. Caspase-1 deficient mice as well as young (12–16 weeks old) vs. aged (18–24 months old) female and male C57BL/6 mice. After induction of metal-DTH, and Cobalt-alloy particle (ASTM F-75, 0.4um median diameter) calvaria challenge, bone resorption was assessed using quantitative micro-computed tomography (micro-CT) analysis and immune responses were assessed by measuring paw inflammation, lymphocyte transformation test (LTT) reactivity and adaptive immune cytokines IFN-gamma and IL-17 (ELISA). Younger aged C57BL/6 female mice exhibited the highest rate and severity of metal sensitivity lymphocyte responses that also translated into higher PIO compared to any other experimental group. The absence of inflammasome/caspase-1 activity significantly suppressed DTH metal-reactivity and osteolysis in both male and female Caspase-1 deficient mice. These murine model results indicate that young female mice are more predisposed to metal-DTH augmented inflammatory responses to wear debris, which is highly influenced by active NLRP3 inflammasome/caspase-1 danger signaling. If these results are clinically meaningful for orthopedic patients, then younger female individuals should be appropriately assessed and followed for DTH derived peri-implant complications.

scholarly journals Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient

2021 ◽  
Author(s):  
Jonathan Klein ◽  
Anderson F. Brito ◽  
Paul Trubin ◽  
Peiwen Lu ◽  
Patrick Wong ◽  
...  
Keyword(s):  
Transplant Recipient ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Primary Infection ◽  
Organ Transplant Recipient ◽  
Solid Organ Transplant Recipient ◽  
Solid Organ ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Immunological Mechanisms

Prior to the emergence of antigenically distinct SARS-CoV-2 variants, reinfections were reported infrequently - presumably due to the generation of durable and protective immune responses. However, case reports also suggested that rare, repeated infections may occur as soon as 48 days following initial disease onset. The underlying immunologic deficiencies enabling SARS-CoV-2 reinfections are currently unknown. Here we describe a renal transplant recipient who developed recurrent, symptomatic SARS-CoV-2 infection - confirmed by whole virus genome sequencing - 7 months after primary infection. To elucidate the immunological mechanisms responsible for SARS-CoV-2 reinfection, we performed longitudinal profiling of cellular and humoral responses during both primary and recurrent SARS-CoV-2 infection. We found that the patient responded to the primary infection with transient, poor-quality adaptive immune responses. The patients immune system was further compromised by intervening treatment for acute rejection of the renal allograft prior to reinfection. Importantly, we also identified the development of neutralizing antibodies and the formation of humoral memory responses prior to SARS-CoV-2 reinfection. However, these neutralizing antibodies failed to confer protection against reinfection, suggesting that additional factors are required for efficient prevention of SARS-CoV-2 reinfection. Further, we found no evidence supporting viral evasion of primary adaptive immune responses, suggesting that susceptibility to reinfection may be determined by host factors rather than pathogen adaptation in this patient. In summary, our study suggests that a low neutralizing antibody presence alone is not sufficient to confer resistance against reinfection. Thus, patients with solid organ transplantation, or patients who are otherwise immunosuppressed, who recover from infection with SARS-CoV-2 may not develop sufficient protective immunity and are at risk of reinfection.

scholarly journals Generation of Mice Deficient for Macrophage Galactose- and N-Acetylgalactosamine-Specific Lectin: Limited Role in Lymphoid and Erythroid Homeostasis and Evidence for Multiple Lectins

2002 ◽  
Vol 22 (14) ◽  
pp. 5173-5181 ◽  
Author(s):  
Thandi M. Onami ◽  
Meei-Yun Lin ◽  
Dawne M. Page ◽  
Shirley A. Reynolds ◽  
Carol D. Katayama ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cd8 T Cells ◽  
Blood Cells ◽  
Mouse Macrophage ◽  
Adaptive Immune Responses ◽  
Targeted Disruption ◽  
Thymic Development ◽  
Adaptive Immune ◽  
Macrophage Receptors ◽  
Deficient Mice

ABSTRACT Macrophage receptors function in pattern recognition for the induction of innate immunity, in cellular communication to mediate the regulation of adaptive immune responses, and in the clearance of some glycosylated cells or glycoproteins from the circulation. They also function in homeostasis by initiating the engulfment of apoptotic cells. Evidence has suggested that macrophage receptors function to recognize cells that are destined for programmed cell death but not yet overtly apoptotic. We have examined the function of a macrophage receptor specific for unsialylated glycoproteins, known as the mouse macrophage galactose- and N-acetylgalactosamine-specific lectin (mMGL) (Ii et al., J. Biol. Chem. 265:11295-11298, 1990; Sato et al., J. Biochem. [Tokyo] 111:331-336, 1992; Yamamoto et al., Biochemistry 33:8159-8166, 1994). With targeted disruption, we tested whether mMGL is necessary for macrophage function, controlled thymic development, the loss of activated CD8 T cells, and the turnover of red blood cells. Evidence indicates that mMGL may play a nonessential role in several of these macrophage functions. Experiments are presented that indicate the existence of another galactose- and N-acetylgalactosamine-recognizing lectin distinct from mMGL. This may explain the absence of a strong phenotype in mMGL-deficient mice.

scholarly journals Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient

2021 ◽  
Author(s):  
Jon Klein ◽  
Anderson Brito ◽  
Paul Trubin ◽  
Peiwen Lu ◽  
Patrick Wong ◽  
...  
Keyword(s):  
Transplant Recipient ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Primary Infection ◽  
Organ Transplant Recipient ◽  
Solid Organ Transplant Recipient ◽  
Solid Organ ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Immunological Mechanisms

Abstract The underlying immunologic deficiencies enabling SARS-CoV-2 reinfections are currently unknown. Here we describe a renal-transplant recipient who developed recurrent, symptomatic SARS-CoV-2 infection 7 months after primary infection. To elucidate the immunological mechanisms responsible for reinfection, we performed longitudinal profiling of cellular and humoral responses during both primary and recurrent SARS-CoV-2 infection. We found that the patient responded to the primary infection with transient, poor-quality adaptive immune responses that was further compromised by intervening treatment for acute rejection of the renal allograft prior to reinfection. Importantly, we identified the development of neutralizing antibodies and humoral memory responses prior to SARS-CoV-2 reinfection. However, these neutralizing antibodies failed to confer protection against reinfection, suggesting that additional factors are required for efficient prevention of SARS-CoV-2 reinfection. Further, we found no evidence supporting viral evasion of primary adaptive immune responses, suggesting that susceptibility to reinfection may be determined by host factors rather than pathogen adaptation.

scholarly journals Disrupting Bordetella Immunosuppression Reveals a Role for Eosinophils in Coordinating the Adaptive Immune Response in the Respiratory Tract

2020 ◽  
Vol 8 (11) ◽  
pp. 1808 ◽  
Author(s):  
Monica C. Gestal ◽  
Uriel Blas-Machado ◽  
Hannah M. Johnson ◽  
Lily N. Rubin ◽  
Kalyan K. Dewan ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Respiratory Tract ◽  
Respiratory Pathogens ◽  
Adaptive Immune Responses ◽  
Eosinophil Recruitment ◽  
Adaptive Immune ◽  
Deficient Mice ◽  
Lymphoid Aggregates ◽  
Allergy And Asthma

Recent findings revealed pivotal roles for eosinophils in protection against parasitic and viral infections, as well as modulation of adaptive immune responses in the gastric mucosa. However, the known effects of eosinophils within the respiratory tract remain predominantly pathological, associated with allergy and asthma. Simulating natural respiratory infections in mice, we examined how efficient and well-adapted pathogens can block eosinophil functions that contribute to the immune response. Bordetella bronchiseptica, a natural pathogen of the mouse, uses the sigma factor btrS to regulate expression of mechanisms that interfere with eosinophil recruitment and function. When btrS is disrupted, immunomodulators are dysregulated, and eosinophils are recruited to the lungs, suggesting they may contribute to much more efficient generation of adaptive immunity induced by this mutant. Eosinophil-deficient mice failed to produce pro-inflammatory cytokines, to recruit lymphocytes, to organize lymphoid aggregates that resemble Bronchus Associated Lymphoid Tissue (BALT), to generate an effective antibody response, and to clear bacterial infection from the respiratory tract. Importantly, the failure of eosinophil-deficient mice to produce these lymphoid aggregates indicates that eosinophils can mediate the generation of an effective lymphoid response in the lungs. These data demonstrate that efficient respiratory pathogens can block eosinophil recruitment, to inhibit the generation of robust adaptive immune responses. They also suggest that some post-infection sequelae involving eosinophils, such as allergy and asthma, might be a consequence of bacterial mechanisms that manipulate their accumulation and/or function within the respiratory tract.

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