Richgels, PK; Yamani, A; Chougnet, CA; Lewkowich, IP. Maternal house dust mite exposure during pregnancy enhances severity of house dust mite-induced asthma in murine offspring. Journal of Allergy and Clinical Immunology. 2017; 140(5):1404-1415.e9.
Early life environmental exposures influences the development of allergic asthma, including those that occur in the prenatal period. House dust mite (HDM) is a powerful, essentially ubiquitous aeroallergen, and there are reports of HDM-derived allergens in amniotic fluid. However, whether maternal exposure to aeroallergens can influence the development of asthma in offspring is unknown. Using a mouse model of HDM-induced allergic asthma, work from the Lewkowich lab demonstrated that HDM exposure during pregnancy markedly exacerbated HDM-induced airway hyperresponsiveness and eosinophilia in offspring. Importantly, maternal HDM exposure did not increase asthma-like symptoms following challenge of offspring with other aeroallergens, demonstrating a level of antigen specificity, yet surprisingly, transfer of HDM-specific immunoglobulins from mother to offspring was not responsible for the observed effects. These observations suggest that maternal HDM exposures may have under-appreciated influences on the overall prevalence of allergic asthma.
Chaton, CT; Herr, AB. Defining the metal specificity of a multifunctional biofilm adhesion protein. Protein Science. 2017; 26(10):1964-1973.
The Herr laboratory has elucidated how a bacterial surface protein uses zinc and copper ions to form adhesive ‘ropes’ between staphylococcal cells in a biofilm. Biofilms are surface-adherent bacterial colonies that are resistant to antibiotics and can cause recurrent infections. The lab found that both several related metal ions can interact with the biofilm adhesion protein, but that only zinc and copper ions can induce assembly of the protein into molecular ropes. The lab had previously shown that chelating zinc to make it unavailable for the staphylococcal bacteria effectively inhibits biofilms from growing. An antimicrobial platform based on their research is being developed for clinical use by Hoth Therapeutics, Inc.
Almanan, M; Raynor, J; Sholl, A; Wang, M; Chougnet, C; Cardin, RD; Hildeman, DA. Tissue-specific control of latent CMV reactivation by regulatory T cells. PLoS pathogens. 2017; 13(8):e1006507-e1006507.
The Hildeman lab uncovered an intriguing role for a suppressive population of T cells, so-called regulatory T cells (Treg) in controlling persistent cytomegalovirus (CMV) infection. CMV is a significant problem in immunosuppressed patients, including those undergoing organ transplantation. In collaboration with Dr. Rhonda Cardin (formerly in the Division of Infectious Diseases) using a mouse model of CMV, they found that Treg play a tissue specific role in controlling latent MCMV infection. Notably, when Treg depletes from mice after the establishment of viral latency, the viral load was significantly reduced in the spleen. Strikingly, in the salivary gland following Treg depletion, the virus emerged from latency and began replicating. Blockade of IL-10 prevented the CMV emergence from latency. Thus, these data show that, depending upon the tissue, Treg can promote or limit latent CMV infection and have consequences for Treg manipulation during organ transplantation.
Yanez, A; Coetzee, SG; Olsson, A; Muench, DE; Berman, BP; Hazelett, DJ; Salomonis, N; Grimes, HL; Goodridge, HS. Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes. Immunity. 2017; 47(5):890-902.e4.
Monocytes are extremely heterogeneous, but the source of these differences is obscure. This study shows that granulocyte-monocyte progenitors (GMP) and monocyte-dendritic cell progenitors (MDP) independently produce functionally distinct inflammatory monocytes, and that microbial stimuli differentially induce these pathways of monocyte production. Notably, monocyte progenitors generated from GMP display “neutrophil-like” gene expression and stimulated LPS; whereas CpG stimulates MDP derived common monocyte progenitors (cMoP).
Rochman, Y; Dienger-Stambaugh, K; Richgels, PK; Lewkowich, IP; Kartashov, AV; Barski, A; Khurana Hershey, GK; Leonard, WJ; Singh, H. TSLP signaling in CD4(+) T cells programs a pathogenic T helper 2 cell state. Science Signaling. 2018; 11(521):eaam8858-eaam8858.
Although T helper 2 (TH2) cells mediate immunity against extracellular parasites, they also promote allergic inflammation. The cytokine interleukin-4 (IL-4), produced by TH2 cells, is also required for their differentiation. Noting the implication of the cytokine TSLP in the pathogenesis of TH2 cell–associated allergic disorders, Dr. Yrina Rochman et al. investigated its role in TH2 cell differentiation. They found that TH2 cells that differentiated in the presence of TSLP and IL-4 produced increased amounts of cytokines and were more pathogenic compared to TH2 cells differentiated in the presence of IL-4 alone. Mice that received CD4+ T cells deficient in the TSLP receptor had reduced allergic responses compared to those that received wild-type cells. Given that pediatric asthma patients had enhanced TH2 cytokine production compared to that of healthy controls, these data suggest that TSLP may be a therapeutic target in allergic diseases.