Major Areas of Research
- Mechanisms of acquired resistance in cutaneous leishmaniasis and those controlling persistent infection
- Study of localized immune circuitries in cutaneous leishmaniasis that allow dermis resident macrophages to maintain M2-like properties as parasitic replicative niches during a strong Th1 environment
- Study of neuro-immune interaction in cutaneous leishmaniasis
- Test of therapeutics targeting dermis resident macrophages during leishmaniasis
Macrophages are considered a critical component of innate immunity against intracellular pathogens. Although macrophages have historically been viewed as monocyte-derived and terminally differentiated cells, recent progress has revealed that many tissue-resident macrophages are embryonically seeded, self-renewed, and perform homeostatic functions associated with M2-like activation programs. There is evidence that tissue-resident macrophages (TRMs) maintain their M2-like phenotype even in an infection-driven pro-inflammatory environment. In this regard, several intracellular pathogens, such as leishmania, are shown to exploit M2-like TRMs as replicative niches to evade pathogen-specific immunity.
Dr. Lee’s primary interests are understanding how the localized circuitries between various neuronal and immune cells, such as sensory neurons, innate lymphoid cells, and eosinophils, allow dermis resident macrophages to maintain M2-like properties and provide replicative niches for parasite growth even in a strong pro-inflammatory environment. This knowledge provides a new perspective to understand the chronicity of infections and develop therapeutic strategies which can selectively target TRMs.
Dr. Lee obtained his Ph.D. from Washington University in St. Louis for studies on the role of IFNg against Listeria infection. After postdoctoral study with Dr. David Sacks, he became a staff scientist in NIAID’s Laboratory of Parasitic Diseases.
Chaves MM, Lee SH, Kamenyeva O, Ghosh K, Peters NC, Sacks D. The role of dermis resident macrophages and their interaction with neutrophils in the early establishment of Leishmania major infection transmitted by sand fly bite. PLoS Pathog. 2020 Nov;16(11):e1008674.
Lee SH, Chaves MM, Kamenyeva O, Gazzinelli-Guimaraes PH, Kang B, Pessenda G, Passelli K, Tacchini-Cottier F, Kabat J, Jacobsen EA, Nutman TB, Sacks DL. M2-like, dermal macrophages are maintained via IL-4/CCL24-mediated cooperative interaction with eosinophils in cutaneous leishmaniasis. Sci Immunol. 2020 Apr;5(46):eaaz4415.
Lee SH, Charmoy M, Romano A, Paun A, Chaves MM, Cope FO, Ralph DA, Sacks DL. Mannose receptor high, M2 dermal macrophages mediate nonhealing Leishmania major infection in a Th1 immune environment. J Exp Med. 2018 Jan;215(1):357-375.