Michelle Reed
e-mail address: reedmi@umich.edu

Mentor: Nicholas Lukacs, PhD

Research Description

Respiratory syncytial virus (RSV) is a ubiquitous human pathogen that produces severe lower respiratory disease in vulnerable individuals, characterized by lung infiltration of innate immune cells and a Th2-skewed adaptive immune response leading to excessive mucus production. RSV-associated bronchiolitis remains the leading cause of hospitalization among infants in the United States, and is responsible for considerable morbidity among patients who are elderly, immune compromised, and those with underlying chronic pulmonary illness. Pulmonary dendritic cells (DCs) direct innate and adaptive immune responses to viral pathogens through secretion of pro-inflammatory cytokines and type I interferon (IFN), as well as through migration and antigen presentation to T cells in lung-draining lymph nodes. In agreement with other studies of virally-infected DCs, work conducted by our laboratory has shown that macroautophagy (autophagy) facilitates TLR-dependent maturation and antigen-presenting cell (APC) function by RSV-infected DCs. The autophagic pathway and its constituent proteins are conversely known to antagonize other pattern recognition receptor (PRR) pathways such as RIG-like receptors (RLRs) and the NLRP3 inflammasome, suggesting a dual role as a negative regulator of inflammatory signaling. Through the use of Beclin-1 haploinsufficient mice and Map1-LC3b-deficient mice, which harbor defects in autophagosome formation, we intend to establish that autophagy within RSV-infected DCs promotes antiviral adaptive immune responses in vivo by driving TLR-mediated production of critical pro-inflammatory cytokines. Additionally, we are examining the antagonistic role of DC-associated autophagy on RLR and inflammasome signaling during RSV infection, and the impact this has on the development of lung pathology in response to RSV.

Publications

Bush S.E., Reed M., Maher S. Impact of forest size on ectoparasite biodiversity: implications for conservation of hosts and parasites. Biodiversity and Conservation, available online April 2013.

Morris S, Swanson MS, Lieberman A, Reed M, Yue Z, Lindell DM, Lukacs NW. Autophagy-mediated dendritic cell activation is essential for innate cytokine production and APC function with respiratory syncytial virus responses. J Immunol. 2011 Oct 15;187(8):3953-61.

Bush SE, Kim D, Reed M, Clayton DH. Evolution of cryptic coloration in ectoparasites. Am Nat. 2010 Oct;176(4):529-35.

Gahring LC, Osborne AV, Reed M, Rogers SW. Neuronal nicotinic alpha7 receptors modulate early neutrophil infiltration to sites of skin inflammation. 
J Neuroinflammation. 2010 Jul 12;7(1):38.

Abstracts

Reed M., Morris S., Jang S., Lukacs N.W. Autophagy-mediated dendritic cell activation modulates T cell cytokine production and pulmonary pathogenesis during respiratory syncytial virus infection. Keystone Symposium on Autophagy in Immunity and Inflammation, Montreal, Quebec, Canada, Feb. 2013.

Reed M., Morris S., Jang S., Lukacs N.W. RSV-induced autophagy in dendritic cells modulates CD4+ T cell cytokine production and pulmonary pathogenesis. 8th annual International Respiratory Syncytial Virus Symposium, Santa Fe, New Mexico, September 2012.

Reed M, Morris S, Lukacs NW. Autophagy in dendritic cells modulates CD4+ T cell cytokine production during RSV infection. Oral and Poster presentation, American Association of Immunologists Immunology 2012. Boston MA, May 2012

Reed M, Morris S, Jang S, Yue Z, Lukacs NW. Autophagy in RSV-infected DC modulates CD4+ T cell cytokine production in vitro.  Poster presentation, Society for Leukocyte Biology annual meeting. Kansas City MO, September 2011.

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Awards

8th Annual Int'l Respiratory Syncytial Virus Symposium Travel Grant, 2013

Rackham Conference Travel Grant, University of Michigan, 2012

Rackham Conference Travel Grant, University of Michigan, 2011