Oral recombinant human or mouse lactoferrin reduces Mycobacterium tuberculosis TDM induced granulomatous lung pathology.
Trehalose 6'6-dimycolate (TDM) is the most abundant glycolipid on the cell wall of Mycobacterium tuberculosis (MTB). TDM is capable of inducing granulomatous pathology in mouse models that resembles those induced by MTB infection. Using the acute TDM model, this work investigates the effect of recombinant human and mouse lactoferrin to reduce granulomatous pathology. C57BL/6 mice were injected intravenously with TDM at a dose of 25 μg·mouse-1. At day 4 and 6, recombinant human or mouse lactoferrin (1 mg·(100 μL)-1·mouse-1) were delivered by gavage. At day 7 after TDM injection, mice were evaluated for lung pathology, cytokine production, and leukocyte populations. Mice given human or mouse lactoferrin had reduced production of IL-12p40 in their lungs. Mouse lactoferrin increased IL-6 and KC (CXCL1) in lung tissue. Increased numbers of macrophages were observed in TDM-injected mice given human or mouse lactoferrin. Granulomatous pathology, composed of mainly migrated leukocytes, was visually reduced in mice that received human or mouse lactoferrin. Quantitation of granulomatous pathology demonstrated a significant decrease in mice given human or mouse lactoferrin compared with TDM control mice. This report is the first to directly compare the immune modulatory effects of both heterologous recombinant human and homologous mouse lactoferrin on the development of TDM-induced granulomas.
a Department of Pathology and Laboratory Medicine, UTHealth McGovern Medical School, Houston, TX 77030, USA.
Shen-An
SA
Hwang
b Department of Integrative Biology and Pharmacology, UTHealth McGovern Medical School, Houston, TX 77030, USA.
Marian L
ML
Kruzel
a Department of Pathology and Laboratory Medicine, UTHealth McGovern Medical School, Houston, TX 77030, USA.
Jeffrey K
JK
Actor
D000284:Administration, Oral; D000818:Animals; D003311:Cord Factors / Q000009:adverse effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006099:Granuloma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007781:Lactoferrin / Q000008:administration & dosage*; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage*; D014376:Tuberculosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D003311:Cord Factors; D016207:Cytokines; C490098:LTF protein, human; C552902:Ltf protein, mouse; D011994:Recombinant Proteins; D007781:Lactoferrin
human lactoferrin; lactoferrine de souris; lactoferrine humaine; mouse lactoferrin; trehalose dimycolate; tréhalose dimycolate