ArticleInfection and immunity2013
Infection with Francisella tularensis LVS clpB leads to an altered yet protective immune response.
Article in Infection and immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Tularemia: Historical Perspectives and Current Challenges of a Re-Emerging Zoonosis.Biomedicines · 2026Review
- Review
- Optimization of single dose VSV-based COVID-19 vaccination in hamsters.bioRxiv : the preprint server for biology · 2021Article
- Hsp100 Molecular Chaperone ClpB and Its Role in Virulence of Bacterial Pathogens.International journal of molecular sciences · 2021Review
- Optimization of Single-Dose VSV-Based COVID-19 Vaccination in Hamsters.Frontiers in immunology · 2021Article
- The ROP16III-dependent early immune response determines the subacute CNS immune response and type III Toxoplasma gondii survival.PLoS pathogens · 2019Article
- ClpB mutants of Francisella tularensis subspecies holarctica and tularensis are defective for type VI secretion and intracellular replication.Scientific reports · 2018Article
- Viable spores of Coccidioides posadasii Δcps1 are required for vaccination and provide long lasting immunity.Vaccine · 2018Article
- Comparative roles of clpA and clpB in the survival of S. Typhimurium under stress and virulence in poultry.Scientific reports · 2018Article
- Live Attenuated Tularemia Vaccines for Protection Against Respiratory Challenge With VirulentFrontiers in cellular and infection microbiology · 2018Review
- Adaptive Immunity toFrontiers in cellular and infection microbiology · 2018Review
- Francisella requires dynamic type VI secretion system and ClpB to deliver effectors for phagosomal escape.Nature communications · 2017Article
- Characterization and Vaccine Potential of Membrane Vesicles Produced by Francisella noatunensis subsp. orientalis in an Adult Zebrafish Model.Clinical and vaccine immunology : CVI · 2017Article
- Efficacy of Resistance toFrontiers in immunology · 2017Article
- Inflammasome-Independent NLRP3 Restriction of a Protective Early Neutrophil Response to Pulmonary Tularemia.PLoS pathogens · 2016Article
- Depletion of alveolar macrophages in CD11c diphtheria toxin receptor mice produces an inflammatory response.Immunity, inflammation and disease · 2015Article
- Francisella tularensis LVS induction of prostaglandin biosynthesis by infected macrophages requires specific host phospholipases and lipid phosphatases.Infection and immunity · 2014Article
- Immune memory-boosting dose of rapamycin impairs macrophage vesicle acidification and curtails glycolysis in effector CD8 cells, impairing defense against acute infections.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Article
- Identification of early interactions between Francisella and the host.Infection and immunity · 2014Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Bacterial attenuation is typically thought of as reduced bacterial growth in the presence of constant immune pressure. Infection with Francisella tularensis elicits innate and adaptive immune responses. Several in vivo screens have identified F. tularensis genes necessary for virulence. Many of these mutations render F. tularensis defective for intracellular growth. However, some mutations have no impact on intracellular growth, leading us to hypothesize that these F. tularensis mutants are attenuated because they induce an altered host immune response. We were particularly interested in the F. tularensis LVS (live vaccine strain) clpB (FTL_0094) mutant because this strain was attenuated in pneumonic tularemia yet induced a protective immune response. The attenuation of LVS clpB was not due to an intracellular growth defect, as LVS clpB grew similarly to LVS in primary bone marrow-derived macrophages and a variety of cell lines. We therefore determined whether LVS clpB induced an altered immune response compared to that induced by LVS in vivo. We found that LVS clpB induced proinflammatory cytokine production in the lung early after infection, a process not observed during LVS infection. LVS clpB provoked a robust adaptive immune response similar in magnitude to that provoked by LVS but with increased gamma interferon (IFN-γ) and interleukin-17A (IL-17A) production, as measured by mean fluorescence intensity. Altogether, our results indicate that LVS clpB is attenuated due to altered host immunity and not an intrinsic growth defect. These results also indicate that disruption of a nonessential gene(s) that is involved in bacterial immune evasion, like F. tularensis clpB, can serve as a model for the rational design of attenuated vaccines.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.