Now at: Nationwide Children’s Hospital and Ohio State School of Medicine (Dept of Pediatrics)

Center for Microbial Pathogenesis
700 Children’s Drive
Columbus, OH 43205

Research Interests:

• To understand the immunological consequences of apoptotic cell clearance during inflammation and infection
• Delineate the role of NADPH oxidase-derived oxidants in immune-regulation

Efficient clearance of apoptotic cells is essential for the maintenance of immunological tolerance, and proper resolution of sterile or microbe-elicited inflammation. During inflammation, macrophages or dendritic cells uptake apoptotic cells, in a process termed  ‘efferocytosis’ leading to the activation of pro-resolution pathways. Inherited mutations, microbial infections, or environmental stressors that dysregulate apoptotic cell clearance, can cause aberrant inflammation and also predispose to chronic inflammatory diseases. I am interested in understanding the transcriptional, metabolic and immunological responses (antigen presentation, inflammatory signaling pathways) of macrophages and dendritic cells during efferocytosis.

The other major lab focus is on understanding the role of NADPH-derived oxidants in modulation of inflammatory responses to periodontal pathogens and sterile inflammation. The phagocyte NADPH oxidase is a multi-subunit enzyme complex that on activation generates superoxide (O₂^-) at the plasma and phagosomal membrane. Superoxide generated is spontaneously or enzymatically converted to multiple forms of Reactive Oxygen Species (ROS) that have anti-microbial and immuno-modulatory functions. Inherited defects in NADPH oxidase subunit alleles that result in complete loss of O₂^- production are associated with chronic granulomatous disease (CGD), an immunodeficiency characterized by life-threatening infections and granulomatous inflammation. Independent of its role in microbial killing, NADPH oxidase also regulates other cellular processes like autophagy, antigen presentation, efferocytosis, and redox-regulation of intracellular proteins. However mechanistic linking oxidants with these processes is largely lacking. Projects in the lab explore the specific role played by oxidants in regulating distinct pathways during the onset and resolution on inflammatory response.

Selected Publications:

1)     Bagaitkar J, Demuth DR and Scott DA. Tobacco use and susceptibility to bacterial infection.  Tob Induc Dis. 2008 Dec 18; 4 (1):12.

2)     Bagaitkar J, Williams LR, Renaud DE, Benakanakere MR, Martin M, Scott DA and Demuth DR. Tobacco induced alterations to Porphyromonas gingivalis– host interactions. Environ Microbiol. 2009 May; 11(5): 1242-53.

3)     Bagaitkar J, Demuth DR, Daep-Amorin C, Renaud DE, Pierce DL and Scott DA. Tobacco upregulated P. gingivalis fimbrial proteins, which induce TLR2 hyposensitivity. PLoS One. 2010 May 4; 5(5): e9323.

4)     Bagaitkar J., Daep CA, Patel CK, Renaud RE, Demuth DR and Scott DA. Tobacco smoke augments Porphyromonas gingivalis-Streptococcus gordonii biofilm formation.PLoS One. 2011; 6(11): e27386. Epub 2011 Nov 14.

5)      BagaitkarJ, Matute JD, Austin A, Arias AA, Dinauer MC.Activation of neutrophil respiratory burst by fungal particles requires phosphatidylinositol 3-phosphate binding to p40^phox in humans but not in mice. Blood. 2012 Oct 18; 120(16): 3385-7.

6)      Zeng MY, Pham D, BagaitkarJ, Liu J, Otero K, Shan M, Wynn TA, Brombacher F, Brutkiewicz RR, Kaplan MH, Dinauer MC.  An efferocytosis-induced, IL-4-dependent macrophage-iNKT cell circuit suppresses sterile inflammation and is defective in murine CGD. Blood. 2013 Apr 25; 121(17): 3473-83.

7)      Bagaitkar J. Cellular Dynamics of resolving inflammation. Blood 2014 Sep 11; 124(11): 1701-3.

8)      Hutcherson JA, Bagaitkar J, Nagano K, Yoshimura F, Wang H, Scott DA. Porphyromonas gingivalis RagB is a proinflammatory signal transducer and activator of transcription 4 agonist. Mol Oral Microbiol. 2015 Jun; 30 (3): 242-52.

9)      Hutcherson JA, Scott DA and Bagaitkar J. Scratching the surface-tobacco-induced biofilms. Tob Induc Dis. 2015 Feb 10; 13(1). (Invited Review)

10)  Bagaitkar J, Nancy K Pech, Stoyan Ivanov, Zeng MY, Guangming Haung and Mary C Dinauer. Dysregulated IL-1α-G-CSF axis exacerbates sterile inflammation in Chronic Granulomatous Disease.  Blood. 2015 Oct 6.

11)  Bagaitkar J, Barbu EA, Perez-Zapata LJ, Austin A, Huang G and Dinauer MC. PI(3)P- p40^phox binding regulates NADPH oxidase activation in mouse macrophages and magnitude of  inflammatory responses in vivo. J. Leukoc Biol. 2016, Aug 19.