Early Clostridium difficile infection during allogeneic hematopoietic stem cell transplantation. Kinnebrew MA, Lee YJ, Jenq RR, Lipuma L, Littmann ER, Gobourne A, No D, vanden Brink M, Pamer EG, Taur Y. PLoS One. 2014 Mar 24;9(3)
Clostridium difficile infection is the most common cause of diarrhea in hospitalized patients. Here, we characterize C. diff infection in patients undergoing hematopoietic stem cell transplantation (HSCT) and its association with graft-versus-host disease.
Quantitative assessment of T cell repertoire recovery after hematopoietic stem cell transplantation. van Heijst JW, Ceberio I, Lipuma L, Samilo DW, Wasilewski GD, Gonzales AM, Nieves JL, van den Brink MR, Perales MA, Pamer EG. Nat Med. 2013 Mar;19(3):372-7.
Humans have immunity to a broad array of pathogens in part because our T cells can recognize roughly 25 million different antigens. But can leukemia and lymphoma patients recover this diverse immunity after receiving a hematopoietic stem cell transplant (HSCT)? Here, we show how T cell populations recover after HSCT and leave patients with different levels of immunity.
Intestinal microbiota containing Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization. Ubeda C, Bucci V, Caballero S, Djukovic A, Toussaint NC, Equinda M, Lipuma L, Ling L, Gobourne A, No D, Taur Y, Jenq RR, van den Brink MR, Xavier JB, Pamer EG. Infect Immun. 2013 Mar;81(3):965-73.
The bacteria that normally reside in our gut do us the favor of preventing pathogenic microbes from infecting us and taking over. This protective function is disrupted, however, when we take antibiotics. Here, we show that replacing the gut flora lost during antibiotic treatment with certain anaerobic bacteria can cure mice of potentially lethal gut infections.
Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice. Ubeda C, Lipuma L, Gobourne A, Viale A, Leiner I, Equinda M, Khanin R, Pamer EG. J Exp Med. 2012 Jul 30;209(8):1445-56.
The immune system greatly influences the composition of the microbes that reside in our intestines, but the mechanism through which this occurs is unclear. Here, we show that mice with defects in certain innate immune signaling molecules develop similar intestinal microbial communities to their littermates that have no immune defects. This suggests that the mechanism for immune influence over gut microbes follows a different pathway.
Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Taur Y, Xavier JB, Lipuma L, Ubeda C, Goldberg J, Gobourne A, Lee YJ, Dubin KA, Socci ND, Viale A, Perales MA, Jenq RR, van den Brink MR, Pamer EG. Clin Infect Dis. 2012
Immunocompromised patients—such as those undergoing allogeneic hematopoietic stem cell transplantation (HSCT)—receive large amounts of antibiotics to prevent infections during their treatment. Here, we show that antibiotics deplete native gut microbes in HSCT patients, allowing pathogenic bacteria to dominate the intestines and in some cases, enter the bloodstream, leading to bacteremia, sepsis, and even death.
Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. Scher JU, Ubeda C, Equinda M, Khanin R, Buischi Y, Viale A, Lipuma L, Attur M, Pillinger MH, Weissmann G, Littman DR, Pamer EG, Bretz WA, Abramson SB. Arthritis Rheum. 2012 Oct;64(10):3083-94.
Rheumatoid arthritis (RA) is a systemic autoimmune disease of almost unknown etiology. We know, however, that autoimmunity is often regulated by crosstalk between immune cells and the microbes that inhabit our bodies. Here, we characterize the oral microbiota of RA patients to determine if specific oral microbial communities are associated with development of RA symptoms.
Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. Jenq RR, Ubeda C, Taur Y, Menezes CC, Khanin R, Dudakov JA, Liu C, West ML, Singer NV, Equinda MJ, Gobourne A, Lipuma L, Young LF, Smith OM, Ghosh A, Hanash AM, Goldberg JD, Aoyama K, Blazar BR, Pamer EG, van den Brink MR. J Exp Med. 2012 May 7;209(5):903-11.
Researchers have recently come to understand that there is a link between inflammation in the gut and the microbes that reside there. Here, we show that patients who undergo allogeneic bone marrow transplants experience dramatic shifts in the composition of their gut microbes. Those shifts can exacerbate or ameliorate post-transplant gut inflammation—a major factor in determining the success of the transplant.
Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile-induced colitis. Buffie CG, Jarchum I, Equinda M, Lipuma L, Gobourne A, Viale A, Ubeda C, Xavier J, Pamer EG. PInfect Immun. 2012 Jan;80(1):62-73.
The intestinal microbiota is a diverse, complex ecosystem. How does this ecosystem change in the presence of antibiotics, and how does that affect susceptibility to infection? Here, we show that a single dose of clindamycin—an antibiotic that kills anaerobic bacteria—profoundly alters the gut microbial ecosystem and increases host susceptibility to Clostridium difficile infection.
Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating toll-like receptor ligands. Shi C, Jia T, Mendez-Ferrer S, Hohl TM, Serbina NV, Lipuma L, Leiner I, Li MO, Frenette PS, Pamer EG. Immunity. 2011 Apr 22;34(4):590-601.
How does the body initiate an immune response when it senses the presence of a pathogen? Here, we show that bacterial antigens, circulating in the blood during an infection, stimulate bone marrow mesenchymal stem cells to produce a chemokine that induces monocyte emigration into the bloodstream.
Toll-like receptor 5 stimulation protects mice from acute Clostridium difficile colitis. Jarchum I, Liu M, Lipuma L, Pamer EG. Infect Immun. 2011 Apr;79(4):1498-503.
Toll-like receptor 5 (TLR5) stimulation activates the innate immune system and maintains the integrity of the intestinal epithelial barrier. Here, we show that by artificially stimulating TLR5, mice are protected from acute Clostridium difficile infection. This could potentially be used as a strategy to prevent C. diff colitis—gut inflammation—in humans.
Inflammatory monocytes facilitate adaptive CD4 T cell responses during respiratory fungal infection. Hohl TM, Rivera A, Lipuma L, Gallegos A, Shi C, Mack M, Pamer EG. Cell Host Microbe. 2009 Nov 19;6(5):470-81.
How do the innate and adaptive immune cells interact during a fungal infection? Here, we show that innate immune cells—inflammatory monocytes—carry fungal antigens to the lymph nodes, prime adaptive helper T cells, and facilitate clearance of the infection.
Essential role for neutrophils but not alveolar macrophages at early time points following Aspergillus fumigatus infection. Mircescu MM, Lipuma L, van Rooijen N, Pamer EG, Hohl TM. J Infect Dis. 2009 Aug 15;200(4):647-56.
What cells are more important in controlling fungal growth right after an infection? Here, we show that neutrophils are essential for preventing fungal growth immediately following infection, but alveolar macrophages are not.
Aberrant tissue localization of fungus-specific CD4+ T cells in IL-10-deficient mice. Rivera A, Collins N, Stephan MT, Lipuma L, Leiner I, Pamer EG. J Immunol. 2009 Jul 1;183(1):631-41.
IL-10 is a protein that acts as an essential immune regulator in the intestinal tract, and mice who can’t produce IL-10 often develop colitis. Here, we show that colitis caused by IL-10 deficiency causes helper T cells to migrate to the gut to control inflammation—even when there is an infection in another area of the body.