Secretory leukocyte protease inhibitor: a secreted pattern recognition receptor for mycobacteria.
BACKGROUND
Human secretory leukocyte protease inhibitor (SLPI) displays bactericidal activity against pathogens such as Escherichia coli and Streptococcus. Furthermore, it has been reported that murine SLPI shows potent antimycobacterial activity.


OBJECTIVE
The aim of the present study was to investigate whether human recombinant SLPI not only kills mycobacteria but also acts as a pattern recognition receptor for the host immune system.


METHODS
For the in vivo experiment, BALB/c mice were infected by intranasal instillation with Mycobacterium bovis BCG and viable BCG load in lung homogenates was later determined. For the in vitro experiments, SLPI was incubated overnight with a suspension of M. bovis BCG or the virulent strain Mycobacterium tuberculosis H37Rv, and the percentage survival as well as the binding of SLPI to mycobacteria was determined. Furthermore, bacteria phagocytosis was also determined by flow cytometry.


RESULTS
Intranasal SLPI treatment decreased the number of colony-forming units recovered from lung homogenates, indicating that SLPI interfered with M. bovis BCG infection. Moreover, SLPI decreased the viability of both M. bovis BCG and H37Rv. We demonstrated that SLPI attached to the surface of the mycobacteria by binding to pathogen-associated molecular pattern mannan-capped lipoarabinomannans and phosphatidylinositol mannoside. Furthermore, we found that in the sputum of patients with tuberculosis, mycobacteria were coated with endogenous SLPI. Finally, we showed that phagocytosis of SLPI-coated mycobacteria was faster than that of uncoated bacteria.


CONCLUSIONS
The present results demonstrate for the first time that human SLPI kills mycobacteria and is a new pattern recognition receptor for them.
Gomez
Sonia A
SA
Department of Pharmacology, University of Buenos Aires School of Medicine, Buenos Aires, Argentina.
Argüelles
Claudia L
CL
Guerrieri
Diego
D
Tateosian
Nancy L
NL
Amiano
Nicolás O
NO
Slimovich
Rut
R
Maffia
Paulo C
PC
Abbate
Eduardo
E
Musella
Rosa M
RM
Garcia
Verónica E
VE
Chuluyan
H Eduardo
HE
D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D010587:Phagocytosis; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000378:metabolism*; D013183:Sputum / Q000737:chemistry / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology
D053481:Secretory Leukocyte Peptidase Inhibitor; C506815:Slpi protein, mouse