TY - JOUR
T1 - Monocyte Locomotion Inhibitory Factor confers neuroprotection and prevents the development of murine cerebral malaria
AU - Galán-Salinas, A.
AU - Corral-Ruíz, G.
AU - Pérez-Vega, M. J.
AU - Fabila-Castillo, L.
AU - Silva-García, R.
AU - Marquina-Castillo, B.
AU - León-Contreras, J. C.
AU - Barrios-Payán, J.
AU - Francisco-Cruz, A.
AU - Montecillo-Aguado, M.
AU - Huerta-Yepez, S.
AU - Calderón-Amador, J.
AU - Flores-Romo, L.
AU - Hernández-Pando, R.
AU - Sánchez-Torres, L. E.
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/8
Y1 - 2021/8
N2 - Cerebral malaria (CM) is a neurological complication derived from the Plasmodium falciparum infection in humans. The mechanisms involved in the disease progression are still not fully understood, but both the sequestration of infected red blood cells (iRBC) and leukocytes and an exacerbated host inflammatory immune response are significant factors. In this study, we investigated the effect of Monocyte Locomotion Inhibitory Factor (MLIF), an anti-inflammatory peptide, in a well-characterized murine model of CM. Our data showed that the administration of MLIF increased the survival and avoided the neurological signs of CM in Plasmodium berghei ANKA (PbA) infected C57BL/6 mice. MLIF administration down-regulated systemic inflammatory mediators such as IFN-γ, TNF-α, IL-6, CXCL2, and CCL2, as well as the in situ expression of TNF-α in the brain. In the same way, MLIF reduced the expression of CD31, CD36, CD54, and CD106 in the cerebral endothelium of infected animals and prevented the sequestration of iRBC and leucocytes in the brain microvasculature. Furthermore, MLIF inhibited the activation of astrocytes and microglia and preserved the integrity of the blood-brain barrier (BBB). In conclusion, our results demonstrated that the administration of MLIF increased survival and conferred neuroprotection by decreasing neuroinflammation in murine CM.
AB - Cerebral malaria (CM) is a neurological complication derived from the Plasmodium falciparum infection in humans. The mechanisms involved in the disease progression are still not fully understood, but both the sequestration of infected red blood cells (iRBC) and leukocytes and an exacerbated host inflammatory immune response are significant factors. In this study, we investigated the effect of Monocyte Locomotion Inhibitory Factor (MLIF), an anti-inflammatory peptide, in a well-characterized murine model of CM. Our data showed that the administration of MLIF increased the survival and avoided the neurological signs of CM in Plasmodium berghei ANKA (PbA) infected C57BL/6 mice. MLIF administration down-regulated systemic inflammatory mediators such as IFN-γ, TNF-α, IL-6, CXCL2, and CCL2, as well as the in situ expression of TNF-α in the brain. In the same way, MLIF reduced the expression of CD31, CD36, CD54, and CD106 in the cerebral endothelium of infected animals and prevented the sequestration of iRBC and leucocytes in the brain microvasculature. Furthermore, MLIF inhibited the activation of astrocytes and microglia and preserved the integrity of the blood-brain barrier (BBB). In conclusion, our results demonstrated that the administration of MLIF increased survival and conferred neuroprotection by decreasing neuroinflammation in murine CM.
KW - Anti-inflammatory
KW - Blood-brain barrier
KW - MLIF
KW - Malaria
KW - Neuroinflammation
KW - Neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=85107052846&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2021.107674
DO - 10.1016/j.intimp.2021.107674
M3 - Artículo
C2 - 34044183
AN - SCOPUS:85107052846
SN - 1567-5769
VL - 97
JO - International Immunopharmacology
JF - International Immunopharmacology
M1 - 107674
ER -