Michael McNehlan
Program: Molecular Microbiology and Microbial Pathogenesis
Current advisor: Christina L. Stallings, PhD
Undergraduate university: University of Colorado-Boulder
Research summary
I studied the role of Sptlc2 in innate immune cells during Mycobacterium tuberculosis (Mtb) infection. SPTLC2 is a component of the enzyme required for the first and rate-limiting step of sphingolipid biosynthesis. Mutations in SPTLC2 can cause a rare neuropathic disease (HSAN1) in humans that is associated with increased risk of infection. However, the immunological basis for increased susceptibility to infection remains unknown. We have found that loss of SPTLC2 in CD11c-expressing innate immune cells results in early death of mice infected with Mtb, establishing SPTLC2 as a novel host determinant of Mtb disease susceptibility. While there are minimal changes to cellular inflammation, there is near complete ablation of alveolar macrophages during Mtb infection in mice that lack SPTLC2 in innate immune cells. We do not detect differences in alveolar macrophage proliferation or death in the absence of SPTLC2 during Mtb infection, but we do see a defect in monocyte differentiation into alveolar macrophage precursor cells by single-cell RNA sequencing. These mice develop a pulmonary alveolar proteinosis-like disease with altered lung gross pathology, elevated surfactant protein concentrations, and hypoxia.
Graduate publications
Hendrix SV, Mreyoud Y, McNehlan ME, Smirnov A, Chavez SM, Hie B, Chamberland MM, Bradstreet TR, Webber AM, Kreamalmeyer D, Taneja R, Bryson BD, Edelson BT, Stallings CL. 2024 BHLHE40 Regulates Myeloid Cell Polarization through IL-10-Dependent and -Independent Mechanisms. J Immunol, 212(11):1766-81.
Feng S, McNehlan ME, Kinsella RL, Sur Chowdhury C, Chavez SM, Naik SK, McKee SR, Van Winkle JA, Dubey N, Samuels A, Swain A, Cui X, Hendrix SV, Woodson R, Kreamalmeyer D, Smirnov A, Artyomov MN, Virgin HW, Wang YT, Stallings CL. 2024 Autophagy promotes efficient T cell responses to restrict high-dose Mycobacterium tuberculosis infection in mice. Nat Microbiol, 9(3):684-97.
Kinsella RL, Nehls EM, Stallings CL. 2018 Roles for Autophagy Proteins in Immunity and Host Defense. Vet Pathol, 55(3):366-373.