B cell subsets are activated and produce cytokines during early phases of Francisella tularensis LVS infection

Plzakova, Lenka; Kubelková, Klára; Kročová, Zuzana; Zárybnická, Lenka; Šinkorová, Zuzana; Macela, Aleš

doi:10.1016/j.micpath.2014.08.009

Cited by 16 publications

(16 citation statements)

References 55 publications

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“…We used mouse B cells expressing the bNAb b12, and showed that there is enhanced activation of these B cells, presumably via avidity gained by the high-density multivalent array. Although the increased secretion of IL-6 from the purified B cells following induction by the trimer-conjugated liposomes was consistent with known cytokine profiles, that TNF alpha secretion was also increased was somewhat surprising as this cytokine is not usually secreted by naïve murine B cells, although it has been reported to be secreted by human B cells (Plzakova et al, 2014)and WEHI B cells(Canfield et al, 2005). This may indicate super-antigen effects by trimer multi-valent array or most likely, an altered cytokine profile in these engineered B cells.…”

Section: Discussionsupporting

confidence: 58%

High-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells

et al. 2016

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A major step towards an HIV-1 vaccine is an immunogen capable of inducing neutralizing antibodies. Envelope glycoprotein (Env). mimetics, such as the NFL and SOSIP designs, generate native-like, well-ordered trimers and elicit tier 2 homologous neutralization (SOSIPs). We reasoned that the display of well-ordered trimers by high-density, particulate array would increase B cell activation compared to soluble trimers. Here, we present the design of liposomal nanoparticles displaying well-ordered Env spike trimers on their surface. Biophysical analysis, cryo- and negative-stain electron microscopy and binding analysis with a panel of broadly neutralizing antibodies confirm high-density, well-ordered trimer particulate array. The Env trimer-conjugated liposomes were superior to soluble trimers in activating B cells ex vivo and germinal center B cells in vivo. In addition, the trimer-conjugated liposomes elicited modest tier 2 homologous neutralizing antibodies. The trimer-conjugated liposomes represent a promising initial lead towards the development of more effective HIV vaccine immunogens.

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Section: Discussionsupporting

confidence: 58%

High-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells

et al. 2016

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“…After infection with F. tularensis, initial immune responses are nonspecific and include macrophage activation followed by later development of cellular and humoral immunity [3,4]. Animal studies have previously shown that B and T cell responses are important in the induction and regulation of an effective immune response to live tularemia vaccines [5,6]; specifically, maintaining either CD4+ or CD8+ T cells in mice appeared to be essential for survival. Animals challenged with virulent Francisella require both T cell subsets for survival [7,8], and in vitro studies of human cells suggest that CD8+ T cell proliferation and cell survival depend on CD4+ proliferation [9].…”

Section: Introductionmentioning

confidence: 99%

Systems Vaccinology for a Live Attenuated Tularemia Vaccine Reveals Unique Transcriptional Signatures That Predict Humoral and Cellular Immune Responses

et al. 2019

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Background: Tularemia is a potential biological weapon due to its high infectivity and ease of dissemination. This study aimed to characterize the innate and adaptive responses induced by two different lots of a live attenuated tularemia vaccine and compare them to other well-characterized viral vaccine immune responses. Methods: Microarray analyses were performed on human peripheral blood mononuclear cells (PBMCs) to determine changes in transcriptional activity that correlated with changes detected by cellular phenotyping, cytokine signaling, and serological assays. Transcriptional profiles after tularemia vaccination were compared with yellow fever [YF-17D], inactivated [TIV], and live attenuated [LAIV] influenza. Results: Tularemia vaccine lots produced strong innate immune responses by Day 2 after vaccination, with an increase in monocytes, NK cells, and cytokine signaling. T cell responses peaked at Day 14. Changes in gene expression, including upregulation of STAT1, GBP1, and IFIT2, predicted tularemia-specific antibody responses. Changes in CCL20 expression positively correlated with peak CD8+ T cell responses, but negatively correlated with peak CD4+ T cell activation. Tularemia vaccines elicited gene expression signatures similar to other replicating vaccines, inducing early upregulation of interferon-inducible genes. Conclusions: A systems vaccinology approach identified that tularemia vaccines induce a strong innate immune response early after vaccination, similar to the response seen after well-studied viral vaccines, and produce unique transcriptional signatures that are strongly correlated to the induction of T cell and antibody responses.

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“…Among the B-lymphocyte (CD19+) subtypes, B1-a lymphocytes, classified as innate lymphocytes, are the best infected by F. tularensis, requiring only the BCR engagement for bacterial internalization, whereas B1-b and B2 lymphocytes are also susceptible to infection, although to a lesser extent; they require the joint participation of BCR and CR1/CR2 receptors for bacterial internalization [63]. B lymphocytes from mice infected with the live vaccine strain of F. tularensis (LVS), especially the B1-a lymphocytes uptake the bacteria; produce numerous proinflammatory cytokines such as IFN-γ, IL-1β, IL-12, IL-17, and TNF-α; decrease amounts of IL-10; and express costimulatory molecules like CD80 and CD86; mice were able to clear bacterial burden 10 days postinfection [129]. Recent studies confirm that the involvement of B lymphocytes is critical for the control of F. novicida infections [130] and that Francisella internalization into B cells requires cell membrane integrity [63].…”

Section: Francisella B-cell Infectionmentioning

confidence: 99%

“…Listeria monocytogenes infection shows an IL-10producing B-cell profile at very early stages of infection, which promotes bacteria persistence and dissemination [179][180][181]. Another example of B lymphocyte-bacteria interaction is the infection caused by F. tularensis which in B cell (particularly B1-a subtype) induces a clearly inflammatory profile characterized by the production of IL1-b, IFNγ, IL-6, IL-12, IL-17, and TNF-α [128,129]. Regarding the activation of the inflammasome complex in B cells infected with Salmonella, it has been described that although this system is functional in B cells, the IL1-β is not secreted because this bacterium inhibits its production by a mechanism of negative regulation of the NLRC4 protein, which favors bacterial intracellular persistence [182].…”

Section: Although B Cells Can Show An Inflammatory Profile In Responsmentioning

confidence: 99%

B Lymphocyte as a Target of Bacterial Infections

Castañeda‐Sánchez¹,

Duarte²,

Domínguez-López³

et al. 2017

Lymphocyte Updates - Cancer, Autoimmunity and Infection

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B lymphocytes are central players in the immune response; canonically, they have been recognized as precursors of antibody-producing cells: plasma cells. Recent findings have shown that the role of B lymphocytes goes far beyond the production of antibodies. There are different subtypes of B lymphocytes with different participations in innate and adaptive responses that include the recognition of the antigen, its processing, and its presentation to T lymphocytes, as well as the production of cytokines that impact and modulate the response toward the pathogen. Traditionally, it has been considered that B lymphocytes do not have phagocytic abilities that allow them to internalize, to process, or even to be infected by bacterial pathogens. The new information has shown that B lymphocytes can be readily infected by bacterial pathogens like Salmonella, Francisella, Moraxella, and Mycobacterium, among others, and respond to those infections. Some of the recent advances on these topics will be presented in this chapter.use of radioactive labels, it was demonstrated that circulating lymphocytes stimulated with antigen were the precursors of antibody-producing cells [15,16], and by the year 1969, the two populations of lymphocytes were identified as T lymphocytes for those thymic-dependent, and those thymic-independent (bursa-equivalent) were referred as B lymphocytes [17].Afterward, it was established in non-avian experimental models that a cooperative response of both lymphocyte species (T and B) was necessary for specific antibody production [18];these observations prompted a large number of studies that recognized the complexity of T-B cooperation, resulting in specific responses to the antigen, including the production of specific high-affinity antibodies [19]. B lymphocytes: a bridge between innate and adaptive immune responsesIt is now known that there are several types of B lymphocytes [20] and that B2 lymphocytes produce specific antibodies during the adaptive response [21]. On the other side, there are also natural antibodies of IgM class mainly [22]; unlike the adaptive antibodies, the natural Lymphocyte Updates -Cancer, Autoimmunity and Infection 150 B Lymphocyte as a Target of Bacterial Infections

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B cell subsets are activated and produce cytokines during early phases of Francisella tularensis LVS infection

Cited by 16 publications

References 55 publications

High-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells

High-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells

Systems Vaccinology for a Live Attenuated Tularemia Vaccine Reveals Unique Transcriptional Signatures That Predict Humoral and Cellular Immune Responses

B Lymphocyte as a Target of Bacterial Infections

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