The Department of Molecular Microbiology and Immunology's (MMI) mission is to maintain active and integrated research programs that study the interactions between microbes and their hosts. The goal is to understand how these influence the outcome of infection and disease progression. Current research interests in the department include understanding host signaling in response to viral infection, molecular mechanisms of NK and NK T cell activation, and molecular principles underlying fungal pathogenesis. This work provides an interdisciplinary structure for our training programs.
MMI supports undergraduate, graduate, and postdoctoral education in the areas of microbiology and immunology. Departmental instruction includes lecture courses, seminar courses, and laboratory research (both undergraduate independent study and graduate thesis). We foster collaborative studies within the department as well as with faculty in other departments, both on campus and hospital-based.
Congratulations to Swathi Penumutchu who has received an NSF Fellowship Award for her work in the Belenky Lab!
Qa-1-Restricted CD8+ T Cells Can Compensate for the Absence of Conventional T Cells during Viral Infection
Anderson et al. describe a heterogenous population of non-classical CD8+ T cells responding to MCMV. Importantly, this population can protect mice from MCMVinduced lethality in the absence of other adaptive immune cells. Among the MHC class Ib-restricted CD8+ T cells responding, Qa-1-specific cells are required for protection.
Shp-2 is critical for ERK and metabolic engagementdownstream of IL-15 receptor in NK cells
The phosphatase Shp-2 was implicated in NK cell development and functions due to itsinteraction with NK inhibitory receptors, but its exact role in NK cells is still unclear. Here weshow, using mice conditionally deficient for Shp-2 in the NK lineage, that NK cell develop-ment and responsiveness are largely unaffected. Instead, wefind that Shp-2 serves mainly toenforce NK cell responses to activation by IL-15 and IL-2. Shp-2-deficient NK cells havereduced proliferation and survival when treated with high dose IL-15 or IL-2. Mechanistically,Shp-2 deficiency hampers acute IL-15 stimulation-induced raise in glycolytic and respirationrates, and causes a dramatic defect in ERK activation. Moreover, inhibition of the ERK andmTOR cascades largely phenocopies the defect observed in the absence of Shp-2. Together,our data reveal a critical function of Shp-2 as a molecular nexus bridging acute IL-15 signalingwith downstream metabolic burst and NK cell expansion.
Cross-Domain and Viral Interactions in the Microbiome
The importance of the microbiome to human health is increasingly recognized and has become a major focus of recent research. However, much of the work has focused on a few aspects, particularly the bacterial component of the microbiome, most frequently in the gastrointestinal tract. Yet humans and other animals can be colonized by a wide array of organisms spanning all domains of life, including bacteria and archaea, unicellular eukaryotes such as fungi, multicellular eukaryotes such as helminths, and viruses. As they share the same host niches, they can compete with, synergize with, and antagonize each other, with potential impacts on their host. Here, we discuss these major groups making up the human microbiome, with a focus on how they interact with each other and their multicellular host.
Coinfection With Influenza A Virus and Klebsiella oxytoca: An Underrecognized Impact on Host Resistance and Tolerance to Pulmonary Infections
The During the influenza season an average of 20% of the human population is infected, with this percentage varying from year to year depending on the virulence of the strains circulating that season. Secondary bacterial pneumonia following influenza A virus (IAV) infection is a serious complication whose prevalence and severity correlates with the virulence of the influenza strain. On average, 0.5% of previously healthy, young individuals and 2.5% of elderly or immunocompromised patients that contract IAV have bacterial coinfections; however, during times of influenza pandemic these numbers climb even higher and in the 1918 influenza virus pandemic up to 6.1% of all patients with IAV were thought to have secondary bacterial infections. In 1918, prior to the use of antibiotics, autopsies confirmed the presence of bacteria in up to 95% of fatalities. In the 2009 pandemic between 18 and 34% of IAV patients in the ICU had a bacterial coinfection and up to 55% of fatalities were associated with bacterial coinfection.