Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels.

T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection. Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2.

Enhanced Macrophage M1 Polarization and Resistance to Apoptosis Enable Resistance to Plague.

Background: Susceptibility to infection is in part genetically driven, and C57BL/6 mice resist various pathogens through the proinflammatory response of their M1 macrophages (MPs). However, they are susceptible to plague. It has been reported elsewhere that Mus spretus SEG mice resist plague and develop an immune response characterized by a strong recruitment of MPs.

T cell expression of IL-18R and DR3 is essential for non-cognate stimulation of Th1 cells and optimal clearance of intracellular bacteria.

Th1 cells can be activated by TCR-independent stimuli, but the importance of this pathway in vivo and the precise mechanisms involved require further investigation. Here, we used a simple model of non-cognate Th1 cell stimulation in Salmonella-infected mice to examine these issues. CD4 Th1 cell expression of both IL-18R and DR3 was required for optimal IFN-γ induction in response to non-cognate stimulation, while IL-15R expression was dispensable.

Contaminated water delivery as a simple and effective method of experimental Salmonella infection.

Aim: In most infectious disease models, it is assumed that gavage needle infection is the most reliable means of pathogen delivery to the GI tract. However, this methodology can cause esophageal tearing and induces stress in experimental animals, both of which have the potential to impact early infection and the subsequent immune response.

Materials & Methods: C57BL/6 mice were orally infected with virulent Salmonella Typhimurium SL1344 either by intragastric gavage preceded by sodium bicarbonate, or by contamination of drinking water.

Salmonella as a model for non-cognate Th1 cell stimulation.

Salmonella has been a model pathogen for examining CD4 T cell activation and effector functions for many years due to the strength of the Th1 cell response observed during Salmonella infections, the relative ease of use of Salmonella, the availability of Salmonella-specific T cell reagents, and the well-characterized nature of the model system, the pathogen, and the immune response elicited. Herein, we discuss the use of Salmonella as a model pathogen to explore the complex interaction of T cells with their inflammatory environment. In particular, we address the issue of bystander activation of naïve T cells and non-cognate stimulation of activated and memory T cells.

Toll-like receptor and inflammasome signals converge to amplify the innate bactericidal capacity of T helper 1 cells.

T cell effector functions can be elicited by noncognate stimuli, but the mechanism and contribution of this pathway to the resolution of intracellular macrophage infections have not been defined. Here, we show that CD4(+) T helper 1 (Th1) cells could be rapidly stimulated by microbe-associated molecular patterns during active infection with Salmonella or Chlamydia. Further, maximal stimulation of Th1 cells by lipopolysaccharide (LPS) did not require T-cell-intrinsic expression of toll-like receptor 4 (TLR4), interleukin-1 receptor (IL-1R), or interferon-γ receptor (IFN-γR) but instead required IL-18R, IL-33R, and adaptor protein MyD88.

Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to recurrent infection.

Typhoid fever is a systemic, persistent infection caused by host-specific strains of Salmonella. Although the use of antibiotics has reduced the complications associated with primary infection, recurrent infection remains an important cause of ongoing human morbidity and mortality. Herein, we investigated the impacts of antibiotic eradication of primary infection on protection against secondary recurrent infection.

Innate immune activation during Salmonella infection initiates extramedullary erythropoiesis and splenomegaly.

Systemic Salmonella infection commonly induces prolonged splenomegaly in murine or human hosts. Although this increase in splenic cellularity is often assumed to be due to the recruitment and expansion of leukocytes, the actual cause of splenomegaly remains unclear. We monitored spleen cell populations during Salmonella infection and found that the most prominent increase is found in the erythroid compartment.

B7-H1 (programmed cell death ligand 1) is required for the development of multifunctional Th1 cells and immunity to primary, but not secondary, Salmonella infection.

Robust Ab and CD4 T cell responses are required for the resolution of Salmonella infection in susceptible mice. In this study, we examined the role of B7-H1 (programmed cell death ligand 1) in resistance to primary Salmonella infection. Infected B7-H1-deficient mice had significantly higher bacterial burdens at day 21 and day 35 postinfection compared with wild-type mice, demonstrating that B7-H1 plays an important role in immunity to Salmonella.