Zika Induces Human Placental Damage and Inflammation
FRONTIERS IN IMMUNOLOGY
Authors: Rabelo, Kissila; de Souza, Luiz Jose; Salomao, Natalia Gedeao; Machado, Lara Nascentes; Pereira, Priscila Gomes; Portari, Elyzabeth Avvad; Basilio-de-Oliveira, Rodrigo; dos Santos, Flavia Barreto; Neves, Laura Dias; Morgade, Luciana Faes; Provance, David William, Jr.; Higa, Luiza Mendonca; Tanuri, Amilcar; de Carvalho, Jorge Jose; Paes, Marciano Viana
Abstract
In Brazil, an epidemic of Zika virus (ZIKV) infections was declared in 2015 that coincided with alarming reports of microcephaly in newborns associated with mother infection. Although the virus has placental tropism, changes in the tissue morphology and immunity of infected patients have not yet been elucidated. Here, we investigated the histopathological and ultrastructural changes along with the immunological profile and the BDNF expression in rare placental material. Tissues were obtained in the 2015-2016 Brazilian epidemic, of ten ZIKV-infected patients during pregnancy, five resulting in cases of fetal microcephaly and five non-microcephaly, compared to five non-infected control placentae. Viral antigens were only detected in samples from the ZIKV infected patients. Infected placentae presented histopathological severe damage, while the ultrastructural evaluation showed abnormal organelles, such as clusters of virus-like particles consistent with the ZIKV dimensions. Increased infiltration of CD68(+)and TCD8(+)cells, expression of MMPs, cytokines (IFN-gamma and TNF-alpha) and other immunological mediators (RANTES/CCL5 and VEGFR-2) confirmed excessive inflammation and vascular permeability dysfunction. An evaluation of BDNF showed a decrease that could modulate neuronal damage in the developing fetus. The placental changes caused by ZIKV are not pathognomonic, however, the data provide evidence that this infection leads to severe placental injury.
Tumor-associated macrophage infiltration and prognosis in colorectal cancer: systematic review and meta-analysis
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
Authors: Li, Jinyuan; Li, Linhai; Li, Yuejin; Long, Yaxin; Zhao, Quan; Ouyang, Yiming; Bao, Weimin; Gong, Kunmei
Abstract
Background Tumor-associated macrophages (TAMs) are key components of colorectal cancer (CRC) microenvironment, but their role in CRC prognosis is not fully defined. Objective This study aimed to evaluate prognostic value of different types and distribution of TAMs in CRC. Methods Total 27 studies with 6115 patients were searched from PubMed and Embase and analyzed to determine the association between TAMs, including distinct TAM subsets and infiltration location, and CRC survival. The prognostic impact of TAMs on CRC was further stratified by tumor type and mismatch repair system (MMR) status. Results A pooled analysis indicated that high density of TAMs in CRC tissue was significantly associated with favorable 5-year overall survival (OS) but not with disease-free survival (DFS). CD 68(+)TAM subset correlated with better 5-year OS, while neither CD68(+)NOS2(+)M1 subset nor CD163(+)M2 subset was correlated with 5-year OS. Increased CD68(+)TAM infiltration in tumor stroma but not in tumor islet predicted improved 5-year OS. Stratification by tumor type and MMR status showed that in colon cancer or MMR-proficient CRC, elevated TAM density was associated with better 5-year OS. Conclusions High infiltration of CD68(+)TAMs could be a favorable prognostic marker in CRC. Future therapies stimulating CD68(+)TAM infiltration may be promising in CRC treatment.