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7131958 
Journal Article 
Lactoferrin Reduces Mycobacterial Trehalose 6,6'-dimycolate Induced M1-type Inflammation and Permits Fluoroquinolone Entry to Granulomas 
Nguyen, TKT; Niaz, Z; D'Aigle, J; Hwang, SA; Kruzel, ML; Actor, JK; , 
2020 
Yes 
Biochemistry and Cell Biology
ISSN: 0829-8211
EISSN: 1208-6002 
English 
32402212 
Primary Mycobacterium tuberculosis (Mtb) infection results in the formation of a densely packed granulomatous response that essentially limits entry and efficacy of immune effector cells. Furthermore, the physical nature of the granuloma does not readily permit entry of therapeutic agents to sites where organisms reside. The Mtb cell wall mycolic acid, trehalose 6,6'-dimycolate (TDM), is a physiologically-relevant molecule to model macrophage mediated events during establishment of the tuberculosis-induced granuloma pathogenesis. No current therapeutic modalities focus to modulate host immune responses to ameliorate tuberculosis disease. Previous studies identified lactoferrin (LF), a natural iron-binding protein proven to modulate inflammation, as able to ameliorate granuloma cohesiveness. Therefore, a series of studies were enabled to further examine the effect of recombinant human LF (rHLF) on histological progression of the TDM-induced pathology. Treatment with rHLF demonstrated significant reduction in size and number of inflammatory foci following TDM injection, with reduced pulmonary pro-inflammatory cytokines TNF-α and IL-1β. LF allowed greater penetration of fluoroquinolone therapeutic to sites of pathology; TDM alone treated mice demonstrated exclusion of ofloxacin to regions of inflammatory response, whereas rHLF treated animals demonstrated increased penetration to responding foci. Finally, recent findings support the hypothesis that this mycobacterial mycolic acid can specifically recruit M1-like polarized macrophages; rHLF treatment was shown to limit the level of this M1-like phenotypic recruitment, corresponding highly with the occurrence of the decreased inflammatory response.