PO Box 9177
- Jung JY, Gleave Parson M, Kraft JD, Lyda L, Kobe B, Davis C, Robinson J, Peña MMO, Robinson CM. Elevated interleukin-27 levels in human neonatal macrophages regulate indoleamine dioxygenase in a STAT-1 and STAT-3-dependent manner. Immunology 2016; 49:35-47. PMID: 27238498
- Cranford TL, Enos RT, Velázquez KT, McClellan JL, Davis JM, Singh UP, Nagarkatti M, Nagarkatti PS, Robinson CM, Murphy EA. Role of MCP-1 on inflammatory processes and metabolic dysfunction following high-fat feedings in the FVB/N strain. Int J Obes. 2015; 40(5):844-51. PMID: 26620890
- Robinson CM, Kobe BN, Schmitt D, Phair B, Gilson T, Jung JY, Roberts L, Liao J, Camerlengo C, Chang B, Davis M, Figurski L, Sindeldecker D, Horzempa J. Genetic engineering of Francisella tularensis LVS for use as a novel live vaccine platform against Pseudomonas aeruginosa infections. Bioengineered 2015; 6:82-8. PMID: 25617059
- Jung, J-Y, Roberts LL, Robinson CM. The presence of interleukin-27 during monocyte-derived dendritic cell differentiation promotes improved antigen processing and stimulation of T cells. Immunology 2015; 144:649-60. PMID: 25346485
- Jung, J-Y, Robinson, CM. IL-12 and IL-27 regulate the phagolysosomal pathway in mycobacteria-infected human macrophages. Cell Commun Signal. 2014; 12:16. PMID: 24618498
- Jung, J-Y, Madan-Lala, R, Georgieva, M, Rengarajan, J, Sohaskey, CD, Bange, F-C, Robinson, CM. The Intracellular environment of human macrophages that produce nitric oxide promotes growth of mycobacteria. Infect. Immun. 2013; 81:3198-209. PMID: 23774601
- Kraft, JD, Horzempa J, Davis C, Jung J-Y, Peña MMO, Robinson, CM. Neonatal macrophages express elevated levels of interleukin-27 that oppose immune responses. Immunology 2013; 139:484-93. PMID: 23464355
- Jung, J-Y, Robinson, CM. Interleukin-27 inhibits phagosomal acidification by blocking vacuolar ATPases. Cytokine 2013; 62:202-5. PMID: 23557795
- Robinson, CM, Jung, J-Y, Nau, GJ. Interferon-g, tumor necrosis factor, and interleukin-18 cooperate to control growth of Mycobacterium tuberculosis in human macrophages. Cytokine 2012; 60:233-41. PMID: 22749533
- Aylwin, CY Ng, Eisenberg, JM, Heath, R J W, Huett, A, Robinson, CM, Nau, GJ, Xavier, RJ. Human leucine-rich repeat (LRR) proteins: a genome-wide bioinformatic categorization and functional analysis in innate immunity. Proceedings of the National Academy of Sciences U.S.A. 2011; 108 Suppl 1:4631-8. PMID: 20616063
- Robinson, CM, O’Dee, D, Hamilton, T, Nau, GJ. Cytokines involved in interferon-γ production by human macrophages. J. Innate Immun. 2010; 2:56-65. PMID: 20375623
- Robinson, CM, Nau, GJ. Interleukin-12 and interleukin-27 regulate macrophage control of Mycobacterium tuberculosis. J. Inf. Dis. 2008; 198:359-66. PMID: 18557702
Microbiology, Immunology & Cell Biology
*The Robinson laboratory is currently accepting students and postdoctoral applications*
Research in the laboratory is focused on the involvement of interleukin (IL)-27 in host immune responses to bacterial infections. IL-27 was first identified as a factor that aids in the initiation of T cell responses and interferon-g production. However, since that time a great deal of evidence has also highlighted immune suppressive activity that is ascribed to IL-27 toward a variety of cell types. Our laboratory predominantly investigates IL-27 as a limiting factor in protective responses during infection and vaccination. This theme is integrated into two well established projects.
The first seeks to understand how IL-27 may contribute to limitations in neonatal and infant immunity. Infections are a major contributor to neonatal and infant mortality and a number of functional differences have been identified between infant and adult immune cells. We have shown IL-27 to be expressed at an elevated level in neonates and infants as compared with adults. Our overarching hypothesis is that IL-27 exhibits immune suppressive activity and may impair immunity in early life. Using age-varied mice we have identified cells that are the primary producers of IL-27 in neonates and infants. Some of these cells are also more abundant in human blood and mouse spleens early in life. Our experiments are currently directed toward understanding the nature of the immunosuppressive activity of IL-27 in conjunction with effector functions from IL-27-producers that contribute to insufficiencies in early life immunity. This approach is tailored toward infections and vaccinations that are particular relevant to neonates. Additional studies seek to understand molecular mechanisms that operate to control different levels of IL-27 expression in different age groups.
A second area of research focus involves human macrophage and dendritic cell (DC) responses to infection by Mycobacterium tuberculosis (Mtb). Tuberculosis is a disease that remains a major threat to global public health. The severity of the epidemic has been intensified by the frequency of coinfection with HIV in developing nations and the emergence of multidrug resistant strains. Numerous cytokines have been shown to play important roles regulating adaptive immune responses to Mtb. The long-term objective of this research is to understand the involvement of IL-27 in human macrophage and dendritic cell responses to mycobacteria and the impact of these responses on the complete immune response. This is important during active infection and in the context of vaccination. The underlying hypothesis is that macrophage and DC responses to IL-27 have important implications in controlling bacterial growth as well as in directing the progression and effectiveness of the immune response to Mtb. Human macrophages express, secrete, and respond to IL-27 during infection by Mtb and the live vaccine strain, BCG. Macrophage responses to both bacteria are improved when IL-27 is neutralized. Under these conditions, the proinflammatory response is elevated and the mycobacterial recovery is significantly reduced. Recent studies have examined the macrophage intracellular environment and effector functions. My laboratory has demonstrated that IL-27 negatively regulates lysosomal acidification. IL-27 also blocks recruitment of intracellular molecules that allow for progression of the phagosome to lysosomes. Consequently, neutralization of IL-27 during infection results in increased colocalization of mycobacteria with host lysosomes. Since antigens that are processed through this pathway associate with MHC class II for surface presentation, this has important implications in the induction of adaptive immunity. We are testing this idea using primary human cells and mouse models of vaccination and aerosol challenge.
Lastly, in collaboration with other colleagues, we are actively developing a new area of research investigating mechanisms that contribute to a link between obesity and development of colon cancer. This area of research focuses on the contributions of chronic inflammation and changes in the gut microbiome that have been associated with obesity. These parameters are explored using a mouse model of high fat diet-induced obesity. We are also extending this research to explore the impact of diet, obesity, chronic inflammation, and changes in gut microbial communities on the susceptibility and severity of enteric infection.