IL-1β-driven NF-κB transcription of ACE2 as a Mechanism of Macrophage Infection by SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), caused by infection with the enveloped RNA betacoronavirus, SARS-CoV-2, led to a global pandemic involving over 7 million deaths. Macrophage inflammatory responses impact COVID-19 severity; however, it is unclear whether macrophages are infected by SARS-CoV-2. We sought to identify mechanisms regulating macrophage expression of ACE2, the primary receptor for SARS-CoV-2, and to determine if macrophages are susceptible to productive infection.

SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure.

SARS-CoV-2 has been shown to cause wide-ranging ocular abnormalities and vision impairment in COVID-19 patients. However, there is limited understanding of SARS-CoV-2 in ocular transmission, tropism, and associated pathologies. The presence of viral RNA in corneal/conjunctival tissue and tears, along with the evidence of viral entry receptors on the ocular surface, has led to speculation that the eye may serve as a potential route of SARS-CoV-2 transmission.

Protection Induced by Oral Vaccination with a Recombinant Delivering LcrV and F1 Antigens in Mice and Rats against Pneumonic Plague.

A newly attenuated Yersinia pseudotuberculosis strain (designated Yptb1) with triple mutation Δ Δ Δ and chromosomal insertion of the Y. pestis operon was constructed as a live vaccine platform. Yptb1 tailored with an Asd plasmid (pYA5199) (designated Yptb1[pYA5199]) simultaneously delivers Y.

Nucleotide receptors mediate protection against neonatal sepsis and meningitis caused by alpha-hemolysin expressing Escherichia coli K1.

Neonatal meningitis-associated Escherichia coli (NMEC) is among the leading causes of bacterial meningitis and sepsis in newborn infants. Several virulence factors have been identified as common among NMEC, and have been shown to play an important role in the development of bacteremia and/or meningitis. However, there is significant variability in virulence factor expression between NMEC isolates, and relatively little research has been done to assess the impact of variable virulence factor expression on immune cell activation and the outcome of infection.

Modification of the Pulmonary MyD88 Inflammatory Response Underlies the Role of the Yersinia pestis Pigmentation Locus in Primary Pneumonic Plague.

Pneumonic plague, caused by , is a rapidly progressing bronchopneumonia involving focal bacterial growth, neutrophilic congestion, and alveolar necrosis. Within a short time after inhalation of , inflammatory cytokines are expressed via the Toll/interleukin-1 (IL-1) adaptor myeloid differentiation primary response 88 (MyD88), which facilitates the primary lung infection. We previously showed that lacking the 102-kb chromosomal pigmentation locus () is unable to cause inflammatory damage in the lungs, whereas the wild-type (WT) strain induces the toxic MyD88 pulmonary inflammatory response.

Activation of Heme Oxygenase Expression by Cobalt Protoporphyrin Treatment Prevents Pneumonic Plague Caused by Inhalation of .

Pneumonic plague, caused by the Gram-negative bacteria , is an invasive, rapidly progressing disease with poor survival rates. Following inhalation of , bacterial invasion of the lungs and a tissue-damaging inflammatory response allows vascular spread of the infection. Consequently, primary pneumonic plague is a multiorgan disease involving sepsis and necrosis of immune tissues and the liver, as well as bronchopneumonia and rampant bacterial growth.

Standardized Method for Aerosol Challenge of Rodents with Yersinia pestis for Modeling Primary Pneumonic Plague.

Primary pneumonic plague occurs when Yersinia pestis is inhaled into the lower respiratory tract where it invades the alveoli and grows. Rapid bacterial growth eventually elicits a neutrophilic inflammatory response that is ineffective and damaging, leading to accelerated progression of disease. In the laboratory, modeling of primary pneumonic plague can be accomplished by instillation of bacterial culture in the nares of anesthetized mice and rats.

Shift from primary pneumonic to secondary septicemic plague by decreasing the volume of intranasal challenge with Yersinia pestis in the murine model.

Yersinia pestis is the causative agent of pneumonic plague, a disease involving uncontrolled bacterial growth and host immunopathology. Secondary septicemic plague commonly occurs as a consequence of the host inflammatory response that causes vasodilation and vascular leakage, which facilitates systemic spread of the bacteria and the colonization of secondary tissues. The mortality rates of pneumonic and septicemic plague are high even when antibiotics are administered.

Yersinia pestis Exploits Early Activation of MyD88 for Growth in the Lungs during Pneumonic Plague.

causes bubonic, pneumonic, and septicemic plague. Although no longer responsible for pandemic outbreaks, pneumonic plague continues to be a challenge for medical treatment and has been classified as a reemerging disease in some parts of the world. In the early stage of infection, inflammatory responses are believed to be suppressed by virulence factors in order to prevent clearance, while later, the hyperactivation of inflammation contributes to the progression of disease.

Induction of Type I Interferon through a Noncanonical Toll-Like Receptor 7 Pathway during Yersinia pestis Infection.

causes bubonic, pneumonic, and septicemic plague, diseases that are rapidly lethal to most mammals, including humans. Plague develops as a consequence of bacterial neutralization of the host's innate immune response, which permits uncontrolled growth and causes the systemic hyperactivation of the inflammatory response. We previously found that host type I interferon (IFN) signaling is induced during infection and contributes to neutrophil depletion and disease.

Macrophage LTB drives efficient phagocytosis of via BLT1 or BLT2.

Unresolved experimental Lyme arthritis in C3H 5-lipoxygenase (5-LOX) mice is associated with impaired macrophage phagocytosis of In the present study, we further investigated the effects of the 5-LOX metabolite, leukotriene (LT)B on phagocytosis of Bone marrow-derived macrophages (BMDMs) from 5-LOX mice were defective in the uptake and killing of from the earliest stages of spirochete internalization. BMDMs from mice deficient for the LTB high-affinity receptor (BLT1) were also unable to efficiently phagocytose Addition of exogenous LTB augmented the phagocytic capability of BMDMs from both 5-LOX and BLT1 mice, suggesting that the low-affinity LTB receptor, BLT2, might be involved. Blocking BLT2 activity with the specific antagonist, LY255283, inhibited phagocytosis in LTB-stimulated BLT1 BMDMs, demonstrating a role for BLT2.

Fractionation Techniques to Examine Effector Translocation.

Many Gram-negative bacterial pathogens use type III secretion systems to export proteins that act directly on the host and aid in the infectious process. Extracellular bacteria primarily rely upon the type III secretion system to insert or inject effector proteins into the cytosol of their host cell in order to perturb intracellular signaling events and aid in pathogenesis. Intracellular bacteria can also depend on the T3SS translocation of effector proteins from vacuolar compartments into the vacuolar membrane or host cell cytosol where they can modulate intracellular trafficking and/or signaling pathways necessary for their growth and survival.

Macrophage Polarization during Murine Lyme Borreliosis.

Infection of C3H mice with Borrelia burgdorferi, the causative agent of Lyme disease, reliably produces an infectious arthritis and carditis that peak around 3 weeks postinfection and then spontaneously resolve. Macrophage polarization has been suggested to drive inflammation, the clearance of bacteria, and tissue repair and resolution in a variety of infectious disease models. During Lyme disease it is clear that macrophages are capable of clearing Borrelia spirochetes and exhausted neutrophils; however, the role of macrophage phenotype in disease development or resolution has not been studied.