Chronic pulmonary bacterial infection facilitates breast cancer lung metastasis by recruiting tumor-promoting MHCII^(hi) neutrophils

Breast cancer can metastasize to various organs,including the lungs.The immune microenvironment of the organs to be metastasized plays a crucial role in the metastasis of breast cancer.Infection with pathogens such as viruses and bacteria can alter the immune status of the lung.However,the effect of chronic inflammation caused by bacteria on the formation of a premetastatic niche within the lung is unclear,and the contribution of specific immune mediators to tumor metastasis also remains largely undetermined.Here,we used a mouse model revealing that chronic pulmonary bacterial infection augmented breast cancer lung metastasis by recruiting a distinct subtype of tumor-infiltrating MHCII^(hi) neutrophils into the lung,which exhibit cancer-promoting properties.Functionally,MHCII^(hi) neutrophils enhanced the lung metastasis of breast cancer in a cell-intrinsic manner.Furthermore,we identified CCL2 from lung tissues as an important environmental signal to recruit and maintain MHCII^(hi) neutrophils.Our findings clearly link bacterial-immune crosstalk to breast cancer lung metastasis and define MHCII^(hi) neutrophils as the principal mediator between chronic infection and tumor metastasis.

Identification of Histoplasma causing an unexplained disease cluster in Matthews Ridge, Guyana

Here,we report the identification of Histoplasma causing an unexplained disease cluster in Matthews Ridge,Guyana.In March 2019,14 employees of Chongqing Bosai Mining Company,China,working in a manganese mining of Guyana,had unexplained fever,and two of them died.We obtained lung and brain tissues as well as the blood samples from the two deceased cases(patient No.1 and 2),and bronchoscopy lavages and cerebrospinal fluid samples from one severe case(patient No.3),respectively.All samples were tested by pathological examination,high-throughput sequencing,and real-time PCR.Pathological detection showed the presence of spore-like structures in the lung tissue of patient No.1,indicating a fungal infection in this patient.Nanopore sequencing identified the existing of H.capsulatum in the lung tissue sample within 13 h.Next-generation sequencing identified specific fragments of H.capsulatum in all of the samples tested(lung,brain and blood serum from the deceased cases,and plasma from the severe case).Real-time PCR assays did not reveal any viral infection related to transmission from bat feces.We conclude that H.capsulatum was the causative pathogen of this disease cluster based on epidemiologic,clinical,pathological and nucleic acid evidence.