Prosper Boyaka - Academia.edu (original) (raw)

Papers by Prosper Boyaka

The Journal of Immunology, 2017

Mucosal IgA or secretory IgA (SIgA) are structurally equipped to resist chemical degradation in t... more Mucosal IgA or secretory IgA (SIgA) are structurally equipped to resist chemical degradation in the harsh environment of mucosal surfaces and enzymes of host or microbial origin. Production of SIgA is finely regulated, and distinct T-independent and T-dependent mechanisms orchestrate Ig α class switching and SIgA responses against commensal and pathogenic microbes. Most infectious pathogens enter the host via mucosal surfaces. To provide a first line of protection at these entry ports, vaccines are being developed to induce pathogen-specific SIgA in addition to systemic immunity achieved by injected vaccines. Mucosal or epicutaneous delivery of vaccines helps target the inductive sites for SIgA responses. The efficacy of such vaccines relies on the identification and/or engineering of vaccine adjuvants capable of supporting the development of SIgA alongside systemic immunity and delivery systems that improve vaccine delivery to the targeted anatomic sites and immune cells.

The Journal of Immunology, May 1, 2014

Cadmium is a toxic heavy metal that can be ingested due to its presence in contaminated water and... more Cadmium is a toxic heavy metal that can be ingested due to its presence in contaminated water and its accumulation in leafy vegetables, fish and grains. Since cadmium can compete with iron for intestinal absorption, long-term ingestion of cadmium can change composition of gut-commensal bacteria by inhibiting the growth of selected bacteria. Gut-commensal bacteria are critical to maintain intestinal homeostasis since they limit attachment of infectious agents, regulate pro-and anti-inflammatory milieu and secretory IgA levels. However, consequences of chronic exposure to cadmium for gut immune homeostasis, and mucosal innate immunity are poorly understood. To investigate the effect of cadmium on gut-homeostasis, C57BL/6 mice were treated with cadmium-contaminated water for 28 days. Mice exposed to cadmium exhibited a significant reduction of secretory IgA levels, which correlated with reduced expression of polymeric Ig receptor mRNA. These mice also showed increased intestinal permeability to macromolecules when compared to control untreated mice. The chronic exposure to cadmium also render these mice more responsive to oral administration of cholera toxin since the frequency of Paneth and goblet cells, as well as the levels of mucus production and anti-microbial mRNA responses seen 16 hours after ingestion of cholera toxin were higher than those of control mice. In summary, environmental pollutant cadmium is a major regulator of gut immune homeostasis and innate immunity.

Proceedings of the National Academy of Sciences, 2021

Alum, used as an adjuvant in injected vaccines, promotes T helper 2 (Th2) and serum antibody (Ab)... more Alum, used as an adjuvant in injected vaccines, promotes T helper 2 (Th2) and serum antibody (Ab) responses. However, it fails to induce secretory immunoglobulin (Ig) A (SIgA) in mucosal tissues and is poor in inducing Th1 and cell-mediated immunity. Alum stimulates interleukin 1 (IL-1) and the recruitment of myeloid cells, including neutrophils. We investigated whether neutrophil elastase regulates the adjuvanticity of alum, and whether a strategy targeting neutrophil elastase could improve responses to injected vaccines. Mice coadministered a pharmacological inhibitor of elastase, or lacking elastase, developed high-affinity serum IgG and IgA antibodies after immunization with alum-adsorbed protein vaccines, including the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). These mice also developed broader antigen-specific CD4+ T cell responses, including high Th1 and T follicular helper (Tfh) responses. Interestingly, in the absence of elastase activity...

Journal of Immunology, 2014

Secretory IgA antibody plays an important role in the protection of mucosal surfaces against micr... more Secretory IgA antibody plays an important role in the protection of mucosal surfaces against microbial pathogens. Induction of the IgA antibody has been known to be largely dependent upon the cytokine milieu. However, the importance of innate immune cell subsets for IgA responses has not been fully appreciated yet. We investigated the role of myeloid cell-subsets on IgA responses to sublingual immunization. In contrast with cholera toxin as an adjuvant which promotes IgA responses, sublingual application of the Bacillus anthracis edema toxin (EdTx) to C57BL/6 mice transiently increased the frequencies of neutrophils in sublingual tissue and cervical lymph nodes (CLNs), and promoted antigen-specific serum IgG, but not serum or mucosal IgA responses. However, EdTx as an adjuvant failed to increase frequencies of neutrophils in sublingual tissue and CLNs of mice lacking IKKβ in myeloid cells (IKKβΔMye), and these mice developed antigen-specific mucosal IgA responses. Interestingly, dep...

Vaccines

Antibiotics are extensively used worldwide for the treatment of common infections by agents such ... more Antibiotics are extensively used worldwide for the treatment of common infections by agents such as E. coli and Salmonella. They also represent the most common cause of alteration of the microbiota in people. We addressed whether broad-spectrum and Gram-negative-targeting antibiotics differentially regulate systemic and mucosal immune responses to vaccines. Antibiotics treatment enhances serum IgG1 responses in mice immunized systemically with a model polyvalent vaccine. This increase was not seen for other IgG subclasses and was dependent on the immunogenicity of vaccine antigens. The broad-spectrum antibiotic cocktail also enhanced serum IgA responses. Interestingly, both the broad spectrum and the antibiotic targeting Gram-negative bacteria enhanced the number of IgA antibody secreting cells in the intestinal lamina propria. This effect was unlikely to be due to an increase in cells expressing gut-homing receptors (i.e., CCR9 and α4β7) in peripheral tissues. On the other hand, th...

SARS-CoV-2 is a worldwide health concern, and new treatment strategies are needed 1. Targeting in... more SARS-CoV-2 is a worldwide health concern, and new treatment strategies are needed 1. Targeting inflammatory innate immunity pathways holds therapeutic promise, but effective molecular targets remain elusive. Here, we show that human caspase-4 (CASP4), and its mouse homologue, caspase-11 (CASP11), are upregulated in SARS-CoV-2 infections, and that CASP4 expression correlates with severity of SARS-CoV-2 infection in humans. SARS-CoV-2-infected Casp11-/- mice were protected from severe weight loss and lung pathology, including blood vessel damage, compared to wild-type (WT) and gasdermin-D knock out (Gsdmd-/-) mice. GSDMD is a downstream effector of CASP11 and CASP1. Notably, viral titers were similar in the three genotypes. Global transcriptomics of SARS-CoV-2-infected WT, Casp11-/- and Gsdmd-/- lungs identified restrained expression of inflammatory molecules and altered neutrophil gene signatures in Casp11-/- mice. We confirmed that protein levels of inflammatory mediators IL-1β, IL6...

Frontiers in Immunology

The prevalence of asthma has been rising steadily for several decades, and continues to be a majo... more The prevalence of asthma has been rising steadily for several decades, and continues to be a major public health and global economic burden due to both direct and indirect costs. Asthma is defined as chronic heterogeneous inflammatory diseases characterized by airway obstruction, mucus production and bronchospasm. Different endotypes of asthma are being recognized based on the distinct pathophysiology, genetic predisposition, age, prognosis, and response to remedies. Mucosal innate response to environmental triggers such as pollen, cigarette smoke, fragrances, viral infection, and house dust mite (HDM) are now recognized to play an important role in allergic asthma. HDM are the most pervasive allergens that co-habitat with us, as they are ubiquitous in-house dusts, mattress and bedsheets, and feed on a diet of exfoliated human skin flakes. Dermatophagoides pteronyssinus, is one among several HDM identified up to date. During the last decade, extensive studies have been fundamental i...

American Journal of Veterinary Research

OBJECTIVE To measure effects of oral Akkermansia muciniphila administration on systemic markers o... more OBJECTIVE To measure effects of oral Akkermansia muciniphila administration on systemic markers of gastrointestinal permeability and epithelial damage following antimicrobial administration in dogs. ANIMALS 8 healthy adult dogs. PROCEDURES Dogs were randomly assigned to receive either A muciniphila (10 9 cells/kg; n = 4) or vehicle (PBS solution; 4) for 6 days following metronidazole administration (12.5 mg/kg, PO, q 12 h for 7 d). After a 20-day washout period, the same dogs received the alternate treatment. After another washout period, experiments were repeated with amoxicillin-clavulanate (13.5 mg/kg, PO, q 12 h) instead of metronidazole. Fecal consistency was scored, a quantitative real-time PCR assay for A muciniphila in feces was performed, and plasma concentrations of cytokeratin-18, lipopolysaccharide, and glucagon-like peptides were measured by ELISA before (T0) and after (T1) antimicrobial administration and after administration of A muciniphila or vehicle (T2). RESULTS A muciniphila was detected in feces in 7 of 8 dogs after A muciniphila treatment at T2 (3/4 experiments) but not at T0 or T1. After metronidazole administration, mean change in plasma cytokeratin-18 concentration from T1 to T2 was significantly lower with vehicle than with A muciniphila treatment (-0.27 vs 2.4 ng/mL). Mean cytokeratin-18 concentration was lower at T1 than at T0 with amoxicillin-clavulanate. No other significant biomarker concentration changes were detected. Probiotic administration was not associated with changes in fecal scores. No adverse effects were attributed to A muciniphila treatment. CONCLUSIONS AND CLINICAL RELEVANCE Detection of A muciniphila in feces suggested successful gastrointestinal transit following oral supplementation in dogs. Plasma cytokeratin-18 alterations suggested an effect on gastrointestinal epithelium. Further study is needed to investigate effects in dogs with naturally occurring gastrointestinal disease.

Biochimica et Biophysica Acta (BBA) - General Subjects

Marijuana consumption is on the rise in the US but the health benefits of cannabis smoking are co... more Marijuana consumption is on the rise in the US but the health benefits of cannabis smoking are controversial and the impact of cannabis components on lung homeostasis is not well-understood. Lung function requires a fine regulation of the ion channel CFTR, which is responsible for fluid homeostasis and mucocilliary clearance. The goal of this study was to assess the effect that exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive substance present in marijuana, has on CFTR expression and function. Cultures of human bronchial epithelial cell line 16HBE14o- and primary human airway epithelial cells were exposed to THC. The expression of CFTR protein was determined by immunoblotting and CFTR function was measured using Ussing chambers. We also used specific pharmacological inhibitors of EGFR and ERK to determine the role of this pathway in THC-induced regulation of CFTR. THC decreased CFTR protein expression in primary human bronchial epithelial cells. This decrease was associated with reduced CFTR-mediated short-circuit currents. THC also induced activation of the ERK MAPK pathway via activation of EGFR. Inhibition of EGFR or MEK/ERK prevented THC-induced down regulation of CFTR protein expression. THC negatively regulates CFTR and this is mediated through the EGFR/ERK axis. This study provides the first evidence that THC present in marijuana reduces the expression and function of CFTR in airway epithelial cells.

Frontiers in immunology, 2018

Intestinal epithelial cells (IECs) are known to regulate allergic sensitization. We addressed the... more Intestinal epithelial cells (IECs) are known to regulate allergic sensitization. We addressed the role of the intrinsic IKKβ signaling in IECs in the effector phase of allergy following oral allergen challenge and its impact on the severity of responses is poorly. Upon orally sensitization by co-administration of ovalbumin with cholera toxin as adjuvant, wild-type and mice lacking IKKβ in IECs (IKKβ mice) developed similar levels of serum IgE and allergen-specific secretory IgA in the gut. However, subsequent allergen challenges in the gut promoted allergic lower responses in KKβ mice. Analysis of cytokines and chemokines in serum and gut tissues after oral allergen challenge revealed impaired eotaxin responses in IKKβ mice, which correlated with lower frequencies of eosinophils in the gut lamina propria. We also determined that IECs were a major source of eotaxin and that impaired eotaxin production was due to the lack of IKKβ signaling in IECs. Oral administration of CCL11 to IKKβ...

Cellular immunology, Jan 11, 2018

Intranasal vaccination of pigs with poly lactic-co-glycolic acid and polyanhydride nanoparticles ... more Intranasal vaccination of pigs with poly lactic-co-glycolic acid and polyanhydride nanoparticles delivered inactivated influenza virus provides cross-reactive T-cell response, but not antibody response, resulting in incomplete protection and no reduction in nasal virus shedding. Expression of BAFF and Th2 transcription factor GATA-3 were downregulated in lungs of pigs vaccinated with influenza nanovaccine, but in mice it upregulated the expression of BAFF and cytokine TGFβ in cervical lymph nodes. However, the intranasal iNKT cell adjuvant, α-Galctosylceramide upregulates the expression of BAFF in pig lungs. In conclusion, expression of BAFF is differentially regulated by intranasal nanovaccine and α-Galctosylceramide in pig respiratory tract.

Comparative immunology, microbiology and infectious diseases, 2016

Cathepsin K (CatK) is an important enzyme regulating bone degradation and has been shown to contr... more Cathepsin K (CatK) is an important enzyme regulating bone degradation and has been shown to contribute to the immune response. We have studied two inflammatory models in equine bone marrow nucleated cells (BMNCs); the LPS and the unmethylated CpG stimulation with the following objectives to: 1.determine whether CatK inhibition will alter the cytokine secretion by stimulated BMNCs; specifically IL-1β, IL-6, and TNF-α, and 2.determine the changes in BMNCs surface markers' expression and MHC II molecule under CatK inhibition. Cathepsin K inhibition promoted BMNCs viability and reduced cell apoptosis. Moreover, CatK inhibition significantly decreased cytokine secretion of either naïve or stimulated BMNCs, and altered their MHC II molecule expression. In conclusion, CatK inhibition in horses did affect BMNCs other than mature osteoclasts rendering them hypo-responsive to both TLR4- and TLR9-induced inflammation, predicting a proteolytic activity for CatK within the MyD88 pathway and/...

The Journal of Immunology, May 1, 2012

The Journal of Immunology, Apr 1, 2011

The Journal of Immunology, 1999

The Journal of Immunology, Apr 1, 2010

The Journal of Immunology, Apr 1, 2007

Blood, Feb 1, 2003

Immunity and MIP-1ß differentially mediate mucosal and systemic Adaptive α MIP-1 (5019 articles) ... more Immunity and MIP-1ß differentially mediate mucosal and systemic Adaptive α MIP-1 (5019 articles) Immunobiology (564 articles) Chemokines, Cytokines, and Interleukins Articles on similar topics can be found in the following Blood collections

The Faseb Journal, Mar 1, 2008