High dose interleukin-12 exacerbates Bordetella pertussis infection and is associated with suppression of cell-mediated immunity in a murine aerosol challenge model

ABSTRACT Despite the availability of efficacious vaccines, the incidence of whooping cough is still high in many countries and is even increasing in countries with high vaccine coverage. Most severe and life-threatening pertussis cases occur in infants who are too young to be sufficiently protected by current vaccine regimens. As a potential solution to this problem, we have developed an attenuated live Bordetella pertussis vaccine strain, named BPZE1. Here, we show that after a single administration, BPZE1 induces dose-dependent protection against challenge with virulent B. pertussis in low-dose and in high-dose intranasal mouse lung colonization models. In addition, we observed BPZE1 dose-dependent antibody titers to B. pertussis antigens, as well as cell-mediated immunity, evidenced by the amounts of gamma interferon (IFN-γ) released from spleen cells upon stimulation with B. pertussis antigens. These two parameters may perhaps be used as readouts in clinical trials in humans that are currently being planned.

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Protective Role of Passively Transferred Maternal Cytokines against Bordetella pertussis Infection in Newborn Piglets

Infection and Immunity ◽

10.1128/iai.01063-16 ◽

2017 ◽

Vol 85 (4) ◽

Cited By ~ 11

Author(s):

Shokrollah Elahi ◽

David R. Thompson ◽

Jill Van Kessel ◽

Lorne A. Babiuk ◽

Volker Gerdts

Keyword(s):

Bordetella Pertussis ◽

Immune Cell ◽

Protective Role ◽

Cell Mediated Immunity ◽

Pertussis Infection ◽

Necrosis Factor Alpha ◽

Specific Antibodies ◽

Newborn Piglets ◽

Wide Range

ABSTRACT Maternal vaccination represents a potential strategy to protect both the mother and the offspring against life-threatening infections. This protective role has mainly been associated with antibodies, but the role of cell-mediated immunity, in particular passively transferred cytokines, is not well understood. Here, using a pertussis model, we have demonstrated that immunization of pregnant sows with heat-inactivated bacteria leads to induction of a wide range of cytokines (e.g., tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], interleukin-6 [IL-6], IL-8, and IL-12/IL-23p40) in addition to pertussis-specific antibodies. These cytokines can be detected in the sera and colostrum/milk of vaccinated sows and subsequently were detected at significant levels in the serum and bronchoalveolar lavage fluid of piglets born to vaccinated sows together with pertussis-specific antibodies. In contrast, active vaccination of newborn piglets with heat-inactivated bacteria induced high levels of specific IgG and IgA but no cytokines. Although the levels of antibodies in vaccinated piglets were comparable to those of passively transferred antibodies, no protection against Bordetella pertussis infection was observed. Thus, our results demonstrate that a combination of passively transferred cytokines and antibodies is crucial for disease protection. The presence of passively transferred cytokines/antibodies influences the cytokine secretion ability of splenocytes in the neonate, which provides novel evidence that maternal immunization can influence the newborn's cytokine milieu and may impact immune cell differentiation (e.g., Th1/Th2 phenotype). Therefore, these maternally derived cytokines may play an essential role both as mediators of early defense against infections and possibly as modulators of the immune repertoire of the offspring.

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BORDETELLA PARAPERTUSSIS VERSUS BORDETELLA PERTUSSIS INFECTION IN CHIDREN: DOES IT REALLY MAKE A DIFFERENCE?

10.26226/morressier.58fa1767d462b80290b514fb ◽

2017 ◽

Author(s):

Afroditi Barmpakou

Keyword(s):

Bordetella Pertussis ◽

Pertussis Infection ◽

Bordetella Parapertussis

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Respiratory Pathogens Identified in Patients with a Clinically Suspected Bordetella Pertussis Infection

SSRN Electronic Journal ◽

10.2139/ssrn.3304295 ◽

2018 ◽

Author(s):

Hassib Narchi ◽

Afaf Alblooshi ◽

Korstiaan Pater ◽

Junu Vazhappully George ◽

Nael Sahhar ◽

...

Keyword(s):

Bordetella Pertussis ◽

Respiratory Pathogens ◽

Pertussis Infection

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HAEMATO-BIOCHEMICAL AND IMMUNOLOGICAL CHANGES IN EXPERIMENTALLY INDUCED ACETAMIPRID TOXICITY IN SWISS ALBINO MICE

THE INDIAN JOURNAL OF VETERINARY SCIENCES AND BIOTECHNOLOGY ◽

10.21887/tijovsab.v12i1.11235 ◽

2016 ◽

Vol 12 (1) ◽

Author(s):

D.T. Fefar ◽

Ankita N. Brahmbhatt ◽

B.P. Joshi ◽

D.J. Ghodasara

Keyword(s):

Dose Level ◽

Significant Rise ◽

High Dose ◽

Cell Mediated Immunity ◽

Swiss Albino Mice ◽

Mean Values ◽

Group Iii ◽

Treatment Groups ◽

Immunological Effects ◽

Albino Mice

A study was conducted on 5 weeks old 64 (32 male and 32 female) Swiss albino mice to assess the haemato-biochemical and immunological effects of acetamiprid. All the male and female mice were randomly divided into eight different groups. The groups I (male) and II (female) served as controls whereas remaining groups served as treatment groups and were administered acetamiprid at the daily dose rate of 20, 10, 5 mg/kg body weight in males(Group III, V, VII) and females (Group IV, VI,VIII),respectively for 28 days. After 28 days treatment, blood samples were collected for hematological, biochemical as well as immunological analysis. There was significant decrease in haematological parameters like Hb, TEC, TLC, neutrophils and lymphocytes count in high dose groups and revealed potential adversity of acetamiprid at rates of 20 mg/kg/day on haematopoetic system of mice. A dose dependent significant rise in mean values of AST and ALT was observed in treatment groups, whereas there was significant decrease in total protein and albumin and increase in BUN in high and mid dose treated groups, irrespective of sex of mice. Dinitroflurobenzene (DNFB) test conducted to assess the cell mediated immunity revealed the toxic effect of acetamiprid on cell mediated immunity of mice at dose level of 10 mg/kg/day. The mice of high dose group revealed a significant decrease in HA titer and indicated the immunotoxic potential of acetamiprid at dose level of 20 mg/kg/day.

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Vitamin D Supplementation Modulates T Cell–Mediated Immunity in Humans: Results from a Randomized Control Trial

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-3599 ◽

2016 ◽

Vol 101 (2) ◽

pp. 533-538 ◽

Cited By ~ 18

Author(s):

Gauree Gupta Konijeti ◽

Pankaj Arora ◽

Matthew R. Boylan ◽

Yanna Song ◽

Shi Huang ◽

...

Keyword(s):

Vitamin D ◽

T Cell ◽

Vitamin D Deficiency ◽

T Cell Activation ◽

Vitamin D3 ◽

Cell Activation ◽

Atp Release ◽

High Dose ◽

Cell Mediated Immunity ◽

Ancillary Study

Abstract Context: Although studies have linked vitamin D deficiency with immune-mediated diseases, data demonstrating a direct effect on T-cell function are sparse. Objective: Our objective was to determine whether oral vitamin D3 influences T-cell activation in humans with vitamin D deficiency. Design: This was a single-center ancillary study within Vitamin D Therapy in Individuals at High Risk of Hypertension, a double-blind, multicenter, randomized controlled trial. Setting: This study was undertaken in a single academic medical center. Participants: Adults with vitamin D deficiency and untreated pre- or early stage I hypertension were included. Intervention: In Vitamin D Therapy in Individuals at High Risk of Hypertension, participants were randomized to either low- (400 IU daily) or high- (4000 IU daily) dose oral vitamin D3 for 6 months. In this ancillary study of 38 patients, we measured CD4+ T-cell activation estimated by intracellular ATP release after stimulation of whole blood with plant lectin phytohemagglutinin collected at baseline (pretreatment) and 2-month follow-up. Main Outcome Measure: Determining whether ATP level changes were significantly different between treatment groups was the main outcome measure. Results: Treatment with 4000 IU of vitamin D3 decreased intracellular CD4+ ATP release by 95.5 ng/ml (interquartile range, −219.5 to 105.8). In contrast, 400 IU of vitamin D3 decreased intracellular CD4+ ATP release by 0.5 ng/ml (interquartile range, −69.2 to 148.5). In a proportional odds model, high-dose vitamin D3 was more likely than low-dose vitamin D3 to decrease CD4+ ATP release (odds ratio, 3.43; 95% confidence interval, 1.06–1.11). Conclusions: In this ancillary study of a randomized controlled trial, we found that high-dose vitamin D3 significantly reduced CD4+ T-cell activation compared to low-dose vitamin D3, providing human evidence that vitamin D can influence cell-mediated immunity.

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Immune responses and protection against Bordetella pertussis infection after intranasal immunization of mice with filamentous haemagglutinin in solution or incorporated in biodegradable microparticles

Vaccine ◽

10.1016/0264-410x(94)00008-b ◽

1995 ◽

Vol 13 (5) ◽

pp. 455-462 ◽

Cited By ~ 72

Author(s):

E Cahill

Keyword(s):

Immune Responses ◽

Bordetella Pertussis ◽

Pertussis Infection ◽

Intranasal Immunization ◽

Biodegradable Microparticles

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Triggering receptor expressed on myeloid cells-1 (TREM-1) contributes to Bordetella pertussis inflammatory pathology

Infection and Immunity ◽

10.1128/iai.00126-21 ◽

2021 ◽

Author(s):

Danisha Gallop ◽

Karen Scanlon ◽

Jeremy Ardanuy ◽

Alexander B. Sigalov ◽

Nicholas H. Carbonetti ◽

...

Keyword(s):

Bordetella Pertussis ◽

Inflammatory Responses ◽

Whooping Cough ◽

Pulmonary Inflammation ◽

Myeloid Cells ◽

Cell Surface Receptor ◽

Bacterial Burden ◽

Emerging Pathogens ◽

Pertussis Infection ◽

Bacterial Control

Whooping cough (pertussis) is a severe pulmonary infectious disease caused by the bacteria Bordetella pertussis . Pertussis infects an estimated 24 million people annually, resulting in >150,000 deaths. The NIH placed pertussis on the list of emerging pathogens in 2015. Antibiotics are ineffective unless administered before the onset of the disease characteristic cough. Therefore, there is an urgent need for novel pertussis therapeutics. We have shown that sphingosine-1-phosphate receptor (S1PR) agonists reduce pertussis inflammation, without increasing bacterial burden. Transcriptomic studies were performed to identify this mechanism and allow for the development of pertussis therapeutics which specifically target problematic inflammation without sacrificing bacterial control. These data suggested a role for triggering receptor expressed on myeloid cells-1 (TREM-1). TREM-1 cell surface receptor functions as an amplifier of inflammatory responses. Expression of TREM-1 is increased in response to bacterial infection of mucosal surfaces. In mice, B. pertussis infection results in TLR9-dependent increased expression of TREM-1 and its associated cytokines. Interestingly, S1PR agonists dampen pulmonary inflammation and TREM-1 expression. Mice challenged intranasally with B. pertussis and treated with ligand-dependent (LP17) and ligand-independent (GF9) TREM-1 inhibitors showed no differences in bacterial burden and significantly reduced TNF-α and CCL-2 expression compared to controls. Mice receiving TREM-1 inhibitors showed reduced pulmonary inflammation compared to controls indicating that TREM-1 promotes inflammatory pathology, but not bacterial control, during pertussis infection. This implicates TREM-1 as a potential therapeutic target for the treatment of pertussis.

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Host and Bacterial Factors Contributing to the Clearance of Colonization by Streptococcus pneumoniae in a Murine Model

Infection and Immunity ◽

10.1128/iai.73.11.7718-7726.2005 ◽

2005 ◽

Vol 73 (11) ◽

pp. 7718-7726 ◽

Cited By ~ 144

Author(s):

Annemarie M. C. van Rossum ◽

Elena S. Lysenko ◽

Jeffrey N. Weiser

Keyword(s):

Streptococcus Pneumoniae ◽

Time Course ◽

Inflammatory Responses ◽

Adaptive Immune Response ◽

Interleukin 12 ◽

Cell Mediated Immunity ◽

T Helper 1 ◽

Independent Manner ◽

Immunodeficient Mice ◽

Human Host Factors

ABSTRACT Nasopharyngeal colonization is the first step in the interaction between Streptococcus pneumoniae (the pneumococcus) and its human host. Factors that contribute to clearance of colonization are likely to affect the spread of the pneumococcus and the rate of pneumococcal disease in the population. To identify host and bacterial factors contributing to this process, we examined the time course of colonization using genetically modified mice and pneumococci. Severe combined immunodeficient mice remained persistently colonized (>6 weeks). Major histocompatibility complex II-deficient mice, but not μMT mice, were unable to clear colonization and showed a diminished T helper 1 response. Thus, CD4+ T cells, rather than the generation of specific antibody, appear to be required for effective Th1-mediated clearance. In addition, the microbial pattern recognition receptor toll-like receptor 2 (TLR2), but not TLR4, was necessary for efficient clearance of colonization. In contrast, no role of complement component 3, inducible nitric oxide synthetase, interleukin 12 (IL-12), or IL-4 could be demonstrated. Expression of the pneumococcal toxin pneumolysin enhanced acute localized inflammatory responses and promoted clearance of colonization in a TLR4-independent manner. We conclude that both innate and CD4+ T-cell-mediated immunity and proinflammatory bacterial factors, rather than a humoral adaptive immune response, are important for clearance of S. pneumoniae from the murine nasopharynx.

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