Differences in innate IFNγ and IL-17 responses to Bordetella pertussis between BALB/c and C57BL/6 mice: role of γδT cells, NK cells, and dendritic cells

Mosley, Yung Yi C.; Lu, Fangjia; HogenEsch, Harm

doi:10.1007/s12026-017-8957-4

Cited by 10 publications

(5 citation statements)

References 59 publications

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“…BALB/c mice also did not show any polarization in CCG profiles towards the Th2 side of the immune spectrum as major Th2 cytokines—IL-4, IL-5, and IL-13—showed similar levels as in C57BL/6 mice. These data fit well with prior studies where BALB/c mice when challenged with a pathogenic agent, showed increased IL-17 but lower Th1 (IFN-γ) cytokine levels compared to C57BL/6 mice ( 62 , 63 ). Overall, our results suggest utilizing C57BL/6 in experiments where an exaggerated Th1 response is needed, such as bacterial or viral infections or to model cancer, while BALB/c could be utilized for experiments where immune homeostasis is a desirable endpoint.…”

Section: Discussionsupporting

confidence: 90%

Host Immunity Influences the Composition of Murine Gut Microbiota

et al. 2022

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The influence of gut microbiota on host immunity is widely studied, and its disturbance has been linked to several immune-mediated disorders. Conversely, whether and how inherently disturbed canonical Th1 (pro-inflammatory) and/or Th2 (anti-inflammatory) immune pathways modify the host microbiome is not sufficiently investigated. Here, we characterized the humoral, cellular, and cytokine immunity, and associated alterations in gut microbiota of naïve wild-type mice (C57BL/6 and BALB/c), and mice with deficiencies in Th2 responses (IL-4Rα and IL-33 knockout mice) or in both Th1 and Th2 responses (NOD scid gamma, NSG mice). A global analysis by de novo clustering of 16S rRNA profiles of the gut microbiota independently grouped wild-type immunocompetent (C57BL/6 and BALB/c), Th2-deficient (IL-4Rα-/- and IL-33-/-), and severely immunodeficient (NSG) mice; where wild-type mice, but not Th2 or severely immunodeficient mice, were enriched in gut bacteria that produce short-chain fatty acids. These include members of phyla Firmicutes, Verrucomicrobia, and Bacteroidetes such as Lactobacillus spp., Akkermansia muciniphila, and Odoribacter spp. Further comparison of the two naïve wild-type mouse strains showed higher microbial diversity (Shannon), primarily linked to higher richness (Chao1), as well as a distinct difference in microbial composition (weighted UniFrac) in BALB/c mice compared to C57BL/6. T-cell and blood cytokine analyses demonstrated a Th1-polarization in naïve adaptive immunity in C57BL/6 animals compared to BALB/c mice, and an expected Th2 deficient cellular response in IL-4Rα-/- and IL-33-/- mice compared to its genetic background BALB/c strain. Together, these data suggest that alterations in the Th1/Th2 balance or a complete ablation of Th1/Th2 responses can lead to major alterations in gut microbiota composition and function. Given the similarities between the human and mouse immune systems and gut microbiota, our finding that immune status is a strong driver of gut microbiota composition has important consequences for human immunodeficiency studies.

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Section: Discussionsupporting

confidence: 90%

Host Immunity Influences the Composition of Murine Gut Microbiota

et al. 2022

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“…6a, c), which is in line with the recent observation that spleenocytes from Balb/c mice produce more IL-17 upon stimulation with B. pertussis antigens than splenocytes from C57BL/6 mice. 40 Long-lived IL-17-producing Th17 memory T cells have also been detected in the respiratory mucosa of B. pertussis-infected baboons, 41 suggesting that the observations made in the mouse model can also be extended to primates. The B. pertussis-specific IL-17-producing memory T cells persisted for at least 2 years after infection of the baboons.…”

Section: Discussionmentioning

confidence: 99%

IL-17-dependent SIgA-mediated protection against nasal Bordetella pertussis infection by live attenuated BPZE1 vaccine

et al. 2018

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BPZE1 is a live attenuated Bordetella pertussis vaccine for nasal administration to mimic the natural route of infection. Here, we studied the mechanism of BPZE1-induced immunity in the murine nasal cavity in contrast to acellular vaccine (aPV), although both vaccines protected against lung colonization. Transfer of splenocytes or serum from BPZE1-vaccinated or aPV-vaccinated mice protected naïve mice against lung colonization but not against nasal colonization. However, transfer of nasal washes from BPZE1-vaccinated mice resulted in protection against nasal colonization, which was lost in IgA-deficient or poly-Ig receptor-deficient mice, indicating that it depends on secretory IgA (SIgA) induction induced in the nose. BPZE1-induced protection against nasal colonization was long-lived despite the relatively rapid decay of SIgA, indicating a potent BPZE1-induced local memory response, likely due to CD4 tissue-resident memory T cells induced in the nose by BPZE1. These cells produced interleukin-17 (IL-17), known to be important for SIgA secretion. Furthermore, BPZE1 failed to protect Il17 mice against nasal colonization by B. pertussis and induced only background levels of nasal SIgA. Thus, our results show important differences in the protective mechanism between the upper and the lower murine respiratory tract and demonstrate an IL-17-dependent SIgA-mediated mechanism of BPZE1-induced protection against B. pertussis nasopharyngeal colonization.

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“…Since BALB/c and C57BL/6 mice have different immune responses to B . pertussis infection and vaccination [ 41 – 43 ], the different genetic backgrounds of two mouse strains and/or the different time points may explain the different observations in these two studies.…”

Section: Discussionmentioning

confidence: 99%

Pertactin contributes to shedding and transmission of Bordetella bronchiseptica

Dewan

Taylor-Mulneix

et al. 2021

PLoS Pathog

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Whooping cough is resurging in the United States despite high vaccine coverage. The rapid rise of Bordetella pertussis isolates lacking pertactin (PRN), a key vaccine antigen, has led to concerns about vaccine-driven evolution. Previous studies showed that pertactin can mediate binding to mammalian cells in vitro and act as an immunomodulatory factor in resisting neutrophil-mediated clearance. To further investigate the role of PRN in vivo, we examined the functions of pertactin in the context of a more naturally low dose inoculation experimental system using C3H/HeJ mice that is more sensitive to effects on colonization, growth and spread within the respiratory tract, as well as an experimental approach to measure shedding and transmission between hosts. A B. bronchiseptica pertactin deletion mutant was found to behave similarly to its wild-type (WT) parental strain in colonization of the nasal cavity, trachea, and lungs of mice. However, the pertactin-deficient strain was shed from the nares of mice in much lower numbers, resulting in a significantly lower rate of transmission between hosts. Histological examination of respiratory epithelia revealed that pertactin-deficient bacteria induced substantially less inflammation and mucus accumulation than the WT strain and in vitro assays verified the effect of PRN on the induction of TNF-α by murine macrophages. Interestingly, only WT B. bronchiseptica could be recovered from the spleen of infected mice and were further observed to be intracellular among isolated splenocytes, indicating that pertactin contributes to systemic dissemination involving intracellular survival. These results suggest that pertactin can mediate interactions with immune cells and augments inflammation that contributes to bacterial shedding and transmission between hosts. Understanding the relative contributions of various factors to inflammation, mucus production, shedding and transmission will guide novel strategies to interfere with the reemergence of pertussis.

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Differences in innate IFNγ and IL-17 responses to Bordetella pertussis between BALB/c and C57BL/6 mice: role of γδT cells, NK cells, and dendritic cells

Cited by 10 publications

References 59 publications

Host Immunity Influences the Composition of Murine Gut Microbiota

Host Immunity Influences the Composition of Murine Gut Microbiota

IL-17-dependent SIgA-mediated protection against nasal Bordetella pertussis infection by live attenuated BPZE1 vaccine

Pertactin contributes to shedding and transmission of Bordetella bronchiseptica

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