Gut Microbial Membership Modulates CD4 T Cell Reconstitution and Function after Sepsis

Cabrera-Pérez, Javier; Babcock, Jeffrey C.; Dileepan, Thamotharampillai; Murphy, Katherine A.; Kucaba, Tamara A.; Badovinac, Vladimir P.; Griffith, Thomas S.

doi:10.4049/jimmunol.1600940

Cited by 33 publications

(34 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neither of these studies examined any elements of the immunophenotype. An elegant study by the Griffith group compared Jax mice to mice from a different vendor following CLP, taking advantage of the fact that these mice differed in whether they had segmented filamentous bacteria (SFB) (34). SFB-specific CD4 + T cells underwent antigen-driven proliferation following sepsis in mice that contained this normal gut microbe but not in genetically identical mice that lacked the microbe.…”

Section: Discussionmentioning

confidence: 99%

The gut microbiome alters immunophenotype and survival from sepsis

Fay¹,

Klingensmith²,

Chen³

et al. 2019

FASEB j.

View full text Add to dashboard Cite

The microbiome is increasingly implicated in immune regulation and mortality from sepsis. Mice with identical genetic backgrounds but distinct microbiomes were obtained from different vendors and analyzed following cecal ligation and puncture (CLP), β diversity of the microbiome measured from feces demonstrated significant differences between The Jackson Laboratory (Jax; Bar Harbor, ME, USA) and Charles River Laboratories (CR; Wilmington, MA, USA) C57/B6 mice. Jax mice had 7‐d mortality of 90% following CLP, whereas CR mice had a mortality of 53%. Differences in vendor were associated with altered immunophenotype with increased splenic IFN‐γ+CD4+ T cells, effector memory CD4+ T cells, and central memory CD4+ T cells and increased Peyer's patch effector memory CD4+ T cells in septic CR mice. To determine whether differences in the microbiome were responsible for these differences, Jax and CR mice were cohoused for 3 wk, after which they assumed a similar microbiota composition. Cohoused mice had improved survival following CLP compared to Jax mice and had similar survival regardless of their vendor of origin. All differences in immunophenotype between septic Jax and CR mice disappeared following cohousing. These findings suggest that the microbiome plays a crucial role in survival and the host immune response from sepsis and represents a potential target for therapeutic intervention.—Fay, K. T., Klingensmith, N. J., Chen, C.‐W., Zhang, W., Sun, Y., Morrow, K. N., Liang, Z., Burd, E. M., Ford, M. L., Coopersmith, C. M. The gut microbiome alters immunophenotype and survival from sepsis. FASEB J. 33, 11258–11269 (2019). http://www.fasebj.org

show abstract

Section: Discussionmentioning

confidence: 99%

The gut microbiome alters immunophenotype and survival from sepsis

Fay¹,

Klingensmith²,

Chen³

et al. 2019

FASEB j.

View full text Add to dashboard Cite

show abstract

“…Specific bacteria play a role in affecting or regulating the immune system (87,88). The composition changes of the gut microbiota have recently been observed in several forms of immunodeficiency in mice (92)(93)(94). Investigation of the population structure and taxonomic or functional features of the microbiota may unfold how gut bacteria regulate the immune system both in patients with PID and healthy individuals.…”

Section: Metagenomicsmentioning

confidence: 99%

Compound Heterozygous Mutations of IL2-Inducible T cell Kinase in a Swedish Patient: the Importance of Early Genetic Diagnosis

et al. 2019

View full text Add to dashboard Cite

Primary immunodeficiency diseases (PIDs) are composed by a group of highly heterogeneous immune system diseases, of which approximately 350 forms of PID have been described so far. The causative gene of around 60% of patients with PIDs has yet unknown. In recent years, Next Generation Sequencing (NGS) has been increasingly adopted for gene identification and molecular diagnosis of rare diseases, including PIDs. An overview of the genetic makeup that underlies PID using NGS has been suggested as a promising approach to elucidate the etiology of PIDs, which could yield diagnostic and, possibly, provide new treatment advances for PID.To approach this goal, we performed either whole exome sequencing (WES, 454 samples) or targeted region sequencing (TRS, 217 samples) on 602 samples of 500 PID pedigrees. We have summarized the practical suggestions for the interpretation of NGS data and the techniques that can be used to search disease-causative PID genes in Paper I. This work aims to improve data annotation, interpretation, and application of NGS data in PIDs, which also facilitates a wide range of application of NGS data analysis in other Mendelian disorders.

show abstract

“…It has been widely reported that TLRs serve important roles in the progression of lung diseases (26). Microbe-derived LPS is suggested to be a major element involved in the development of sepsis (28). In general, LPS triggers inflammatory responses by activating TLRs, which then recruit neutrophils to the inflammatory site (25,29).…”

Section: Discussionmentioning

confidence: 99%

Reduced peripheral blood miR‑140 may be a biomarker for acute lung injury by targeting Toll‑like receptor4 (TLR4)

Wang

Guo

et al. 2018

Exp Ther Med

View full text Add to dashboard Cite

Abstract. Acute lung injury (ALI) is a common complication of sepsis to which patients often succumb due to poor effective pharmacological interventions. Recent studies have focused on the potential application of circulating microRNAs (miRs or miRNAs) as novel prognostic and therapeutic biomarkers. The present study focuses mainly on miR-140, the role of which is poorly understood in the progression of ALI. The results of the present study revealed that toll-like receptor 4 (TLR4) expression was upregulated the lungs of rats with ALI. Meanwhile, serum levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-1β were significantly increased in rats with ALI compared with normal control rats. These data indicated the successful establishment of LPS-induced ALI. Furthermore, miR-140 was decreased in the peripheral blood of patients with ALI compared with control subjects. Receiver operator characteristic analysis indicated that miR-140 could be used to screen ALI patients and distinguish them from healthy controls. MiR-140 was demonstrated to be downregulated in the plasma and lungs of rats with ALI compared with the normal control group. A dual luciferase reporter assay indicated that TLR4 was a target gene of miR-140. To investigate whether miR-140 exerted its role via TLR4, a specific TLR4-targeting small interfering RNA was selected. It was revealed that TLR4 silencing was able to suppress the phosphorylation of NF-κB even in cells transfected with miR-140 inhibitor. In summary, reduced miR-140 expression and increased TLR4 signaling activation may serve a key role in the progression of ALI.

show abstract

Gut Microbial Membership Modulates CD4 T Cell Reconstitution and Function after Sepsis

Cited by 33 publications

References 37 publications

The gut microbiome alters immunophenotype and survival from sepsis

The gut microbiome alters immunophenotype and survival from sepsis

Compound Heterozygous Mutations of IL2-Inducible T cell Kinase in a Swedish Patient: the Importance of Early Genetic Diagnosis

Reduced peripheral blood miR‑140 may be a biomarker for acute lung injury by targeting Toll‑like receptor4 (TLR4)

Contact Info

Product

Resources

About