Associate Professor of Microbiology and Immunology
B.S. California Lutheran University
Ph.D. University of California, Los Angeles
June Round's Lab Page
June Round's PubMed Literature Search
Molecular Biology Program
Host-Commensal Bacterial Interactions
The mammalian immune system is charged with the task of recognizing microbial molecules and subsequently coordinating pathogen clearance. However, humans are host to a multitude of symbiotic microorganisms called the microbiota. This diverse consortium of bacteria take up residence on almost all environmentally exposed surfaces of the body, with the greatest diversity and number of organisms residing within the gastrointestinal (GI) tract. Since both pathogenic and commensal microorganisms share similar molecular patterns, it remains unclear how host immune responses toward symbiotic bacteria are prevented. Inflammatory bowel disease (IBD) results from a loss of host tolerance to commensal bacteria, thus understanding the mechanisms by which the host tolerates the microbiota and in turn how the microbiota influences the host immune system is paramount toward gaining a deeper understanding of mucosal biology and developing therapies for the treatment of intestinal disease.
Interests in the lab include: 1) Understanding how T cell intrinsic Toll like receptor (TLRs) signaling governs T cell responses and how this impacts host tolerance toward the microbiota. 2) Identification and characterization of novel host genes within mucosal T cells regulated by the microbiota. 3) Understand how commensal organisms are able to regulate the host adaptive immune system and impact disease states.
In an effort to understand how commensal micro-organisms shape host immune responses we have focused our investigations on a prominent human commensal organism, Bacteriodes fragilis. We use animals raised in a completely sterile environment (called germ-free mice) as a model host organism. In this way we can associate the animals with a single species of bacteria and determine how these organisms are able to influence host immune system development. B.fragilis synthesizes a capsular polysaccharide, called polysaccharide A (PSA). We have found that either colonization with B. fragilis or treatment with purified PSA can protect animals from experimental models of inflammatory bowel disease. We have further identified that PSA is recognized by the host immune system via toll-like receptor 2 (TLR2). Toll like receptors (TLRs) are surface proteins that detect conserved molecular patterns on micro-organisms. TLR function has long been thought to be primarily restricted to innate immune cells (macrophages and dendritic cells). However, more recent studies have demonstrated that T lymphocytes express a variety of TLRs. How TLR signaling impacts the function of T cells remains completely unclear. We have recently demonstrated that the ability of PSA to elicit host anti-inflammatory activity is directly mediated through TLR2 signaling on a T cell (Round,et.al., Science,2011). Additionally, we have found that this signaling pathway is utilized by B.fragilis to colonize its host. Thus, while TLR signaling is currently thought to result in the elimination of pathogenic organisms, we have identified a commensal bacteria that can exploit the TLR pathway to promote intestinal colonization.
Bacteriodes Fragilis lying in close proximity to host intestinal tissue. This image was taken by a technique called whole mount confocal microscopy. This image is the top of intestinal layer that lies closest to the lumen of the intestine. Epithelial cell nuclei appear in blue and the outer surface of the cell membrane is red. B.fragilis is shown in green .
- Petersen C, Bell R, Klag KA, Lee SH, Soto R, Ghazaryan A, Buhrke K, Ekiz HA, Ost KS, Boudina S, O'Connell RM, Cox JE, Villanueva CJ, Stephens WZ, Round JL. T cell-mediated regulation of the microbiota protects against obesity. Science. 2019 Jul 26;365(6451).
- Brown DG, Soto R, Yandamuri S, Stone C, Dickey L, Gomes-Neto JC, Pastuzyn ED, Bell R, Petersen C, Buhrke K, Fujinami RS, O'Connell RM, Stephens WZ, Shepherd JD, Lane TE, Round JL. The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling. Elife. 2019 Jul 16;8. pii: e47117.
- Gogokhia L, Buhrke K, Bell R, Hoffman B, Brown DG, Hanke-Gogokhia C, Ajami NJ, Wong MC, Ghazaryan A, Valentine JF, Porter N, Martens E, O'Connell R, Jacob V, Scherl E, Crawford C, Stephens WZ, Casjens SR, Longman RS, Round JL. Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis. Cell Host Microbe. 2019 Feb 13;25(2):285-299.e8.
- Chiaro TR, Round JL. Fiber Puts Lactobacillus to SLEep. Cell Host Microbe. 2019 Jan 9;25(1):3-5.
- Gomes-Neto JC, Round JL. Gut microbiota: a new way to take your vitamins. Nat Rev Gastroenterol Hepatol. 2018 Sep;15(9):521-522.
- Ost KS, Round JL. Communication Between the Microbiota and Mammalian Immunity. Annu Rev Microbiol. 2018 Sep 8;72:399-422. doi: 10.1146/annurev-micro-090817-062307. Epub 2018 Jun 21. Review.
- Weis AM, Soto R, Round JL. Commensal regulation of T cell survival through Erdr1. Gut Microbes. 2018;9(5):458-464. Review.
- Brown DG, Round JL. Friends in Low Places: Intestinal Commensals Limit Colitis through Molecular Mimicry. Cell. 2017 Oct 19;171(3):503-505.
- Ost KS, Round JL. A Few Good Commensals: Gut Microbes Use IFN-γ to Fight Salmonella. Immunity. 2017 Jun 20;46(6):977-979.
- Soto R, Petersen C, Novis CL, Kubinak JL, Bell R, Stephens WZ, Lane TE, Fujinami RS, Bosque A, O'Connell RM, Round JL. Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor. Proc Natl Acad Sci U S A. 2017 May 23;114(21):5497-5502.
- Chiaro TR, Soto R, Zac Stephens W, Kubinak JL, Petersen C, Gogokhia L, Bell R, Delgado JC, Cox J, Voth W, Brown J, Stillman DJ, O'Connell RM, Tebo AE, Round JL. A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice. Sci Transl Med. 2017 Mar 8;9(380). pii: eaaf9044. doi: 10.1126/scitranslmed.aaf9044. Erratum in: Sci Transl Med. 2017 May 3;9(388):.
- Kubinak JL, Round JL. Do antibodies select a healthy microbiota? Nat Rev Immunol. 2016 Dec;16(12):767-774.
- Wallace J, Hu R, Mosbruger TL, Dahlem TJ, Stephens WZ, Rao DS, Round JL, O'Connell RM. Genome-Wide CRISPR-Cas9 Screen Identifies MicroRNAs That Regulate Myeloid Leukemia Cell Growth. PLoS One. 2016 Apr 15;11(4):e0153689.
- Kubinak JL, Stephens WZ, Soto R, Petersen C, Chiaro T, Gogokhia L, Bell R, Ajami NJ, Petrosino JF, Morrison L, Potts WK, Jensen PE, O'Connell RM, Round JL. MHC variation sculpts individualized microbial communities that control susceptibility to enteric infection. Nat Commun. 2015 Oct 23;6:8642.
- Petersen C, Round JL (2014) Defining dysbiosis and its influence on host immunity and disease. Cellular Microbiology 16(7):1024-33
- Novis CL, Archin NM, Buzon MJ, Verdin E, Round JL, Lichterfeld M, Margolis DM, Planelles V, Bosque A (2013) Reactivation of latent HIV-1 in central memory CD4⁺ T cells through TLR-1/2 stimulation. Retrovirology 10:119
- Hu R, Huffaker TB, Kagele DA, Runtsch MC, Bake E, Chaudhuri AA, Round JL, O'Connell RM (2013) MicroRNA-155 confers encephalogenic potential to Th17 cells by promoting effector gene expression. Journal of Immunology 190(12):5972-80
- Huffaker TB, Hu R, Runtsch MC, Bake E, Chen X, Zhao J, Round JL, Baltimore D, O'Connell RM (2012) Epistasis between microRNAs 155 and 146a during T cell-mediated antitumor immunity. Cell Reports 2(6):1697-709
- Humphries LA, Shaffer MH, Sacirbegovic F, Tomassian T, McMahon KA, Humbert PO, Silva O, Round JL, Takamiya K, Huganir RL, Burkhardt JK, Russell SM, Miceli MC (2012) Characterization of in vivo Dlg1 deletion on T cell development and function. PLoS One 7(9):e45276
- Kubinak JL, Round JL. Toll-like receptors promote mutually beneficial commensal-host interactions (2012) PLOS Pathogens 8(7):e1002785
- Round JL, Lee SM, Li J, Tran G, Jabri B, Chatila TA, Mazmanian SK (2011) The Toll like receptor pathway establishes commensal gut colonization. Science 332(6032):974-977
- O'Connell RM, Kahn D, Gibson W, Round JL, Chaudhuri AA, Rao DS, Baltimore D (2010) MicroRNA-155 promotes autoimmune inflammation by enhancing production of inflammatory cytokines. Immunity 33(4):607-619
- Round JL, SK Mazmanian (2010) Inducible Foxp3+ regulatory T cell development by a commensal bacterium of the intestinal microbiota. PNAS 107(27):12204-9
- Round JL, O'Connell RM, Mazmanian SK (2010) Coordination of tolerogenic immune responses by the commensal microbiota. Journal of Autoimmunity 34(3):J220-5
- Round JL, Mazmanian SK (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nature Reviews Immunology. May 9; 313-323.
- Mazmanian SK, Round JL, Kasper D (2008) A microbial symbiosis factor prevents inflammatory disease. Nature 453 (7195):602-4
- Round JL, Humphries LA, Tomassian T, Mittelstadt P, Zhang M, Miceli MC (2007) Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-?B transcription factors. Nature Immunology 8(2): 154-160