Charisse Petersen

University of British Columbia | UBC · Michael Smith Laboratories

Significance Little is known about the molecular mechanisms by which the microbiota influences T-cell responses. We have determined that a secreted protein, Erdr1, is highly upregulated in germfree T cells and that microbial products can suppress Erdr1 through MyD88. Erdr1 functions to induce apoptosis through a Fas-dependent pathway that can impac...

The presentation of protein antigens on the cell surface by major histocompatibility complex (MHC) molecules coordinates vertebrate adaptive immune responses, thereby mediating susceptibility to a variety of autoimmune and infectious diseases. The composition of symbiotic microbial communities (the microbiota) is influenced by host immunity and can...

Altered commensal communities are associated with human disease. IgA mediates intestinal homeostasis and regulates microbiota composition. Intestinal IgA is produced at high levels as a result of T follicular helper cell (TFH) and B cell interactions in germinal centers. However, the pathways directing host IgA responses toward the microbiota remai...

Mammalian immune system development depends on instruction from resident commensal micro-organisms. Diseases associated with abnormal immune responses toward environmental and self antigens have been rapidly increasing over the last fifty years. These diseases include inflammatory bowel disease (IBD), multiple sclerosis (MS), type I diabetes (T1D),...

Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the microorganisms and their genes within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the conformation of the microbiome may deter...

Background Early antibiotic exposure is linked to persistent disruption of the infant gut microbiome and subsequent elevated pediatric asthma risk. Breastfeeding acts as a primary modulator of the gut microbiome during early life, but its effect on asthma development has remained unclear. Methods We harnessed the CHILD cohort to interrogate the in...

Background/Objective The steep rise in childhood obesity has emerged as a worldwide public health problem. The first 4 years of life are a critical window where long-term developmental patterns of body mass index (BMI) are established and a critical period for microbiota maturation. Understanding how the early-life microbiota relate to preschool gr...

Secretory immunoglobulin A (SIgA) in human milk plays a central role in complex maternal-infant interactions that influence long-term health outcomes. Governed by genetics and maternal microbial exposure, human milk SIgA shapes both the microbiota and immune system of infants. Historically, SIgA-microbe interactions have been challenging to unravel...

Fecal-oral contamination promotes malnutrition pathology. Lasting consequences of early life malnutrition include cognitive impairment, but the underlying pathology and influence of gut microbes remain largely unknown. Here, we utilize an established murine model combining malnutrition and iterative exposure to fecal commensals (MAL-BG). The MAL-BG...

The practice of rearing cows and calves together is gaining popularity on dairy farms, with different systems currently under assessment in mainland Europe, the United Kingdom, and Oceania. Research into the effects of cow–calf rearing has primarily focused on direct health and welfare implications, and little work has examined the role of differen...

Recent evidence suggests an immunomodulatory role for commensal fungi (mycobiota) in the gut, yet little is known about the composition and dynamics of early-life gut fungal communities. In this work, we show for the first time that the composition of the gut mycobiota of Canadian infants changes dramatically over the course of the first year of li...

Bacterial members of the infant gut microbiota and bacterial-derived short-chain fatty acids (SCFAs) have been shown to be protective against childhood asthma, but a role for the fungal microbiota in asthma etiology remains poorly defined. We recently reported an association between overgrowth of the yeast Pichia kudriavzevii in the gut microbiota...

Microbiota maturation and immune development occur in parallel with, and are implicated in, allergic diseases, and research has begun to demonstrate the importance of prenatal influencers on both. Here, we investigate the meconium metabolome, a critical link between prenatal exposures and both early microbiota and immune development, to identify co...

IgA mediates microbial homeostasis at the intestinal mucosa. Within the gut, IgA acts in a context-dependent manner to both prevent and promote bacterial colonization and to influence bacterial gene expression, thus providing exquisite control of the microbiota. IgA–microbiota interactions are highly diverse across individuals and populations, yet...

Purpose of review: The microbiome and immune system are intrinsically linked, and during infancy these crucial biological systems undergo a concurrent and expansive maturation process. As these maturation processes progress, some children develop a sequence of IgE-mediated immune disorders termed the 'Allergic March', and unfortunately the prevale...

Nonalcoholic fatty liver disease (NAFLD) remains a global epidemic, but it is often studied in the context of obesity and aging. Nutritional deficits, however, also trigger hepatic steatosis, influencing health trajectories in undernourished pediatric populations. Here, we report that exposure to specific gut microbes impacts fatty liver pathology...

Immunoglobulin (Ig) A controls host-microbial homeostasis in the gut. IgA recognition of beneficial bacteria is decreased in acutely undernourished children, but the factors driving these changes in IgA targeting are unknown. Child undernutrition is a global health challenge that is exacerbated by poor sanitation and intestinal inflammation. To und...

Background Childhood asthma incidence is decreasing in some parts of Europe and North America. Antibiotic use in infancy has been associated with increased asthma risk. In the present study, we tested the hypothesis that decreases in asthma incidence are linked to reduced antibiotic prescribing and mediated by changes in the gut bacterial community...

T cells help keep you lean The gut microbiota is a critical factor regulating mammalian metabolism. The host immune system, in turn, can shape the microbiome, in part via immunoglobulin A (IgA) antibodies. Petersen et al. report that mice defective in T follicular helper cell development and gut IgA production show hallmarks of metabolic syndrome w...

Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or anim...

Identifying regulatory mechanisms that influence inflammation in metabolic tissues is critical for developing novel metabolic disease treatments. Here, we investigated the role of microRNA-146a (miR-146a) during diet-induced obesity in mice. miR-146a is reduced in obese and type 2 diabetic patients and our results reveal that miR-146a-/- mice fed a...

miR-146a and BAT weight and gene expression. (A-C) qRT-PCR expression data from BAT samples of young, untreated WT (blue) or miR-146a-/- (green) mice relative to L32 expression in (A) BAT activation genes, (B) Lipogenesis genes, and (C) inflammatory immune genes. (D) Weight (g) of BAT samples from WT or miR-146a-/- mice. (E) qRT-PCR expression of m...

miR-146a protects against high blood glucose levels during diet-induced obesity but does not alter pancreatic architecture. (A) WT and miR-146a-/- mice on NCD or HFD were injected with glucose at 0 minutes and blood glucose levels were measured over time for 120 minutes. (B) Blood glucose of 6-hour fasted WT and miR-146a-/- mice on NCD or HFD. (C)...

GSEA of RNA-seq data from miR-146a-/- and WT mouse ATMs on NCD or HFD. (A) Percentages of live, singlet CD45+ cells positive for CD11b and F4/80 markers, collected from the SVF of VAT in WT and miR-146a-/- mice fed NCD or HFD. (B) Total number of live, singlet, CD45+ cells positive for CD11b and F4/80 markers, collected from the SVF of VAT in WT an...

Underlying numeric data. (XLSX)

miR-146a is required to prevent weight gain and Leptin accumulation during HFD. (A) Each line shows average percent weight gain over time during an individual experimental repeat of young female WT (blue) and miR-146a-/- (red) mice on HFD. (B) Percent weight gain over time of WT and miR-146a-/- mice on NCD. (C) Body weight gain (in grams) over time...

Increased weight gain by miR-146a-/- mice during DIO is not dependent upon miR-155. (A) Percent weight gain over time of diet in WT, miR-155-/-, miR-146a-/-, and DKO mice on HFD. (B) Body weight (in grams) of WT, miR-155-/-, miR-146a-/-, and DKO mice over time of diet. (C) Blood glucose levels of WT, miR-155-/-, miR-146a-/-, and DKO mice following...

Materials table listing all materials used in this publication. (PDF)

Infection with the bacteria Borrelia burgdorferi results in a multidimensional disease including, fever, headache, arthritis, and a characteristic skin rash. When left untreated, bacteria can disseminate to multiple parts of the body including joints, heart, and nervous system. Approximately 10–20% of patients treated with antibiotic therapy for Ly...

T cells predominate the immune responses in the synovial fluid of patients with persistent Lyme arthritis; however, their role in Lyme disease remains poorly defined. Using a murine model of persistent Lyme arthritis, we observed that bystander activation of CD4+ and CD8+ T cells leads to arthritis-promoting IFN-γ, similar to the inflammatory envir...

Asthma is an aberrant inflammatory condition of the airways affecting approximately 1 in 10 children in affluent countries. An increasing body of evidence suggests that microbial exposures during a "critical window" of development in early life play a central role in determining future asthma susceptibility. However, like the disease itself, consid...

The commensal microbiota has an important impact on host health, which is only beginning to be elucidated. Despite the presence of fungal, archaeal, and viral members, most studies have focused solely on the bacterial microbiota. Antibodies against the yeast Saccharomyces cerevisiae are found in some patients with Crohn’s disease (CD), suggesting t...

Supplementary Figures 1-7 and Supplementary Tables 1-6

Host-microbial interactions within the mammalian intestines must be properly regulated in order to promote host health and limit disease. Because the microbiota provide constant immunological signals to intestinal tissues, a variety of regulatory mechanisms have evolved to ensure proper immune responses to maintain homeostasis. However, many of the...

Saccharomyces cerevisiae Spt6 protein is a conserved chromatin factor with several distinct functional domains including a natively unstructured 30 residue N-terminal region that binds competitively with Spn1 or nucleosomes. To uncover physiological roles of these interactions, we isolated histone mutations that suppress defects caused by weakening...

The 20S proteasome is an essential, 28-subunit protease that sequesters proteolytic sites within a central chamber, thereby repressing substrate degradation until proteasome activators open the entrance/exit gate. Two established activators, Blm10 and PAN/19S, induce gate opening by binding to the pockets between proteasome α-subunits using C-termi...

FACT plays important roles in both gene transcription and DNA replication. However, how this protein complex is targeted to these two distinct cellular processes remains largely unknown. Here we show that ubiquitylation of the Spt16 subunit of FACT by Rtt101, the cullin subunit of an E3 ubiquitin ligase in Saccharomyces cerevisiae, links FACT to DN...

The p53 tumor suppressor protein is a critical checkpoint in prevention of tumor formation, and the function of p53 is dependent on proper formation of the active tetramer. In vitro studies have shown that p53 binds DNA most efficiently as a tetramer, though inactive p53 is predicted to be monomeric in vivo. We demonstrate that FlAsH binding can be...