Effect of Lactoferrin to Increase Drug Permeability of Primary Pulmonary Mycobacterial Granulomas

<p>Despite extensive research and worldwide eradication efforts, Mycobacterium tuberculosis (<em>Mtb</em>) remains a major infectious pathogen to the human population with about 10 million cases of infection per year globally. The host-pathogen interaction, pulmonary granuloma formation, and <em>Mtb</em> adaptions result in increased complexity of the disease. Granulomas are formed by active immune responses generated during <em>Mtb</em> infection, and serve to contain and limit bacterial dissemination. The major mycobacterial surface mycolic acid, trehalose 6,6'-dimycolate (TDM), functions in multiple ways to enhance immune cell recruitment of sites of infection, to induce inflammation and granulomatous responses, and to initiate survival strategies for the organism inside macrophages. <em>Mtb</em> also benefits from establishment of a tightly formed granuloma, which both protects it from immune reactivity and serves as a physical boundary to limit penetration of drugs during therapeutic treatment. In order to demystify the complicated relationship between the host and pathogen, many studies have been performed around the primary <em>Mtb</em>-induced granuloma to combat the challenges that come with this specific immunopathology. We hypothesized that by altering the immunopathology of granulomas using lactoferrin, an immunomodulating agent, it will allow greater penetration of therapeutics into the site of focal inflammation. Our lab has reported that oral bovine lactoferrin treatments during the innate immune response leads to significant modulation of the primary <em>Mtb</em> granuloma response and lessen <em>Mtb</em> burden in mouse lungs. Here, we show that such modulation during granuloma development can also be achieved by using recombinant human lactoferrin oral treatments to increase granuloma permeability and promotes drug penetration in both TDM-induced granulomatous inflammation as well as during active <em>Mtb</em>-infection. Findings from this work show lactoferrin’s potential as a host-directed therapeutic that can be combined with current TB standard treatment to reduce pathological damage in the lungs post mycobacterial infection.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2021

Authors dc:creator

• Nguyen, Thao
• Nguyen, Thao KT
• <p>0000-0002-8272-5819</p>

Contributors dc:contributor

• Jeffrey K. Actor, Ph.D.
• Marian L. Kruzel, Ph.D.
• Robert L. Hunter, M.D. Ph.D.

• Lactoferrin
• Mycobacterium tuberculosis
• Mtb
• trehalose 6
• 6'-dimycolate
• TDM
• granuloma
• immunomodulating
• drug penetration
• inflammation
• permeability
• therapeutics.
• Analytical, Diagnostic and Therapeutic Techniques and Equipment
• Biological Phenomena, Cell Phenomena, and Immunity
• Medical Immunology
• Medicine and Health Sciences
• Therapeutics

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1134

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2180