B cell-deficient mice are susceptible to infection by Pneumocystis carinii f. sp. muris (PC). To determine whether this susceptibility is due a requirement for cells prime T cells, we compared CD4 cell responses PC in bone marrow chimeric that express MHC class II (MHCII) on all APCs (wild-type (WT) chimeras) and MHCII except (MHCII(-/-) chimeras). Although was rapidly cleared WT mice, levels remained high lacked cells. In addition, although were primed the draining lymph nodes of MHCII(-/-)...

The burden of tuberculosis and cardiovascular disease (CVD) is enormous worldwide. CVD rates are rapidly increasing in low- middle-income countries. Public health programs have been challenged with the overlapping epidemics. Monocyte/macrophages, lymphocytes cytokines involved cellular mediated immune responses against Mycobacterium also main drivers atherogenesis, suggesting a potential pathogenic role via mechanisms that described for other pathogens establish chronic infection latency....

Thrombocytopenia is associated with many viral infections suggesting virions interact and affect platelets. Consistently, particles are seen inside platelets, platelet activation markers detected in viremic patients. In this article, we sought mechanistic insights into these virion/platelet interactions by examining how platelets endocytose, traffic, activated a model virion. Approach Results: Using fluorescently tagged HIV-1 pseudovirions, 3-dimensional structured illumination microscopy,...

Long COVID is the overarching name for a wide variety of disorders that may follow diagnosis acute SARS-COVID-19 infection and persist weeks to many months. Nearly every organ system be affected.We report nine patients suffering with 101 547 days. All exhibited significant perturbations their immune systems, but only one was known immunodeficient prior studies directed at evaluating them possible treatment. Neurological cardiac symptoms were most common. Based on this data other evidence...

ABSTRACT Infection with mucoid strains of Pseudomonas aeruginosa in chronic inflammatory diseases the airway is difficult to eradicate and can cause excessive inflammation. The roles alternatively activated regulatory subsets macrophages this pathophysiological process are not well characterized. We previously demonstrated that azithromycin induces an macrophage-like phenotype vitro . In present study, we tested whether affects macrophage activation status migration lungs P. -infected mice....

Abstract Both CD4+ T cells and B are critical for defense against Pneumocystis carinii infection; however, the mechanism by which mediate protection is unknown. We show that P. carinii-specific IgM not sufficient to clearance of from lungs since CD40-deficient mice produced normal levels specific IgM, but were unable clear organisms. Using chimeric in deficient CD40 (CD40KO chimeras) we found infection delayed compared with wild-type controls. These CD40KO did produce class-switched IgG or...

To determine whether different antibody isotypes associated with T helper 1 (Th1) or Th2 responses are protective against Pneumocystis carinii, mice disrupted interleukin 4 genes (IL-4(-/-) mice) gamma interferon (IFN-gamma(-/-) along wild-type C57BL/6 were immunized intratracheally P. depleted of cells in vivo by use monoclonal antibodies, and rechallenged 10(7) viable carinii organisms. Nearly all resolved their lung infections (limit detection, log10 4.06) within 21 days challenge even...

Tuberculosis has been associated with an increased risk of cardiovascular disease (CVD), including acute myocardial infarction (AMI). We investigated whether latent tuberculosis infection (LTBI) is AMI. conducted a case-control study in 2 large national public hospital networks Lima, Peru, between July 2015 and March 2017. Case patients were first time diagnosis type 1 (spontaneous) Controls without history excluded known human immunodeficiency virus infection, disease, or prior LTBI...

Tissue-resident memory CD8 T cells are a unique subset of virus-specific CTLs that bolster local immune responses after becoming lodged in previously infected tissues. These provide enhanced protection by intercepting returning pathogens before new infection gets established. In contrast, central circulate the bloodstream and proliferate secondary lymphoid organs replenishing effector cell populations remote parts body. Both participate immunity to influenza virus infection; however,...

SUMMARY Several pathogens have been associated with increased cardiovascular disease (CVD) risk. Whether this occurs Mycobacterium tuberculosis infection is unclear. We assessed if the risk of acute myocardial infarction (AMI). identified patients index claims from a large de-identified database ~15 million adults enrolled in U.S. commercial insurance policy between 2008 and 2010. Tuberculosis were 1:1 matched to without using propensity scores. compared occurrence AMI non-tuberculosis...

Abstract B cells play a critical role in the clearance of Pneumocystis. In addition to production Pneumocystis-specific Abs, are required during priming phase for CD4+ T expand normally and generate memory. Clearance Pneumocystis was found be dependent on Ag specific ability secrete Ab, as mice with defective these functions or restricted BCR were unable control infection. Because antiserum only able partially protect cell–deficient from infection, we hypothesized that optimal cell requires...

The role of gamma interferon (IFN-gamma) in host defense to Pneumocystis carinii was investigated by use three different murine models infection. C57BL/6 scid/scid (severe combined immunodeficient [SCID]) mice were given intratracheal inoculations P. and reconstituted with splenocytes from either disrupted IFN-gamma genes (IFN-gamma-/- mice) or homozygous wild-type (IFN-gamma+/+) mice. Unreconstituted SCID had log10 7.08 +/- 0.13 nuclei their lungs at day 22 postinfection, whereas...

Pulmonary eosinophilia is one of the most consistent hallmarks asthma. Infiltration eosinophils into lung in experimental asthma dependent on adhesion molecule vascular cell molecule-1 (VCAM-1) endothelial cells. Ligation VCAM-1 activates NADPH oxidase, which required for VCAM-1-dependent leukocyte migration vitro. To examine whether endothelial-derived oxidase modulates eosinophil recruitment vivo, mice deficient (CYBB mice) were irradiated and received wild-type hematopoietic cells to...

Influenza virus is a significant cause of mortality and morbidity in children; however, little known about the T cell response infant lungs. Neonatal mice are highly vulnerable to influenza only control very low doses virus. We compared infection between infected as adults or at 2 d old observed defective migration into lungs neonatal mice. In adult mice, numbers cells lung interstitia peaked 10 postinfection, whereas infiltration, activation, expression TNF-alpha was delayed until wk...

ABSTRACT The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists a trophic stage and an ascus-like cystic stage. Infection with cyst induces proinflammatory immune responses, while forms suppress cytokine response to multiple pathogen-associated molecular patterns (PAMPs), including β-glucan. A targeted gene expression assay was used evaluate dendritic cell following stimulation alone, normal mixture cysts, or We demonstrate that downregulated genes normally...

Abstract Host responses to Pneumocystis carinii infection mediate impairment of pulmonary function and contribute the pathogenesis pneumonia. IL-10 is known inhibit inflammation reduce severity pathology caused by a number infectious organisms. In present studies, IL-10-deficient (IL-10 knockout (KO)) mice were infected with P. determine whether efficiency clearance organisms could be altered in absence IL-10. The kinetics from KO was significantly enhanced compared that wild-type (WT) mice....

Abstract Neonatal mice have a delayed CD4-mediated inflammatory response to Pneumocystis carinii (PC) infection in the lungs that corresponds TNF-α and clearance of organisms compared with adult mice. Since is known drive up-regulation adhesion molecules, we examined expression function molecules neonatal The both ICAM-1 VCAM-1 was significantly lower PC-infected adults. Additionally, migration T cells across endothelial expressing monocyte chemotactic protein-1 aberrant cells, although α4β1...

Abstract Initiation of the pulmonary inflammatory response to Pneumocystis carinii is delayed by 3 wk in mice infected as neonates compared with adults. There was no difference proliferative draining lymph node T cells from adults when stimulated vitro either Con A or anti-CD3 mAb. However, TNF-α and IFN-γ mRNA expression lungs P. carinii-infected significantly lower than indicating a lack appropriate activation signaling local environment. This may have been due active suppression because...

Alveolar macrophages are the effector cells largely responsible for clearance of Pneumocystis carinii from lungs. Binding organisms to beta-glucan and mannose receptors has been shown stimulate phagocytosis organisms. To further define mechanisms used by alveolar P. carinii, mice deficient in expression scavenger receptor A (SRA) were infected with was monitored over time. SRA-deficient (SRAKO) consistently cleared faster than did wild-type control mice. Expedited corresponded elevated...