Mansour Mohamadzadeh

The University of Texas Health Science Center at San Antonio

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Yong Ge

The University of Texas Health Science Center at San Antonio

Jennifer L. Owen

University of Florida

Mojgan Zadeh

The University of Texas Health Science Center at San Antonio

Bikash Sahay

University of Florida

Jürgen Knop

Johannes Gutenberg University Mainz

Todd R. Klaenhammer

North Carolina State University

Yaíma L. Lightfoot

National Institutes of Health

Joachim Saloga

Johannes Gutenberg University Mainz

Mojgan Zadeh

The University of Texas Health Science Center at San Antonio

Tao Yang

Chuzhou University

Cooperative Institutions

University of Florida

105

Florida College

Johannes Gutenberg University Mainz

United States Army Medical Research Institute of Infectious Diseases

The University of Texas Southwestern Medical Center

Emory University

Northwestern University

The University of Texas Health Science Center at San Antonio

National Institutes of Health

Tulane University

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Fibroblastic Reticular Cell Infection by Hemorrhagic Fever Viruses

Immunotherapy (2009)

Keith E. Steele Arthur O. Anderson Mansour Mohamadzadeh

Viral hemorrhagic fevers (VHFs) often cause high mortality with high infectivity, multiorgan failure, shock and hemorrhagic diathesis. Fibroblastic reticular cells (FRCs) within secondary lymphoid organs provide a supporting scaffold to T-lymphocyte areas. These cells regulate the movement of various immune cells and soluble molecules that promote T-lymphocyte homeostasis. We previously reported Ebola virus infection of FRCs, but ascribed little significance to this finding. Here, we studied infection of FRCs by Ebola, Marburg and Lassa viruses. We demonstrate that FRCs, or the extracellular 'conduit' of the fibroblastic reticulum of nonhuman primates, are targets of Ebola, Marburg and Lassa viruses. Furthermore, we observed that FRC damage correlates temporally and spatially with lymphocyte damage and that FRCs serve as nidi of fibrin deposition. In addition, we show that nonhuman primate FRCs express p75 NGF receptor and tissue transglutaminase. Our data suggest that viral infection of FRCs may be crucial to the immunological dysfunction and coagulopathy characteristic of VHFs. We further propose that p75 NGF receptor and tissue transglutaminase may be involved in FRC-associated dysfunction during the course of infection.

Lassa fever

Reticular cell

Lassa virus

10.2217/1750743x.1.2.187

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Citations (29)

The gut microbiota transfers the therapeutic effect of inhibiting glucose metabolism in lupus-prone mice

The Journal of Immunology (2022)

Ahmed S. Elshikha Josephine Brown Nathalie Kanda Yong Ge Xiangyu Teng

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease in which autoantibodies induce tissue damage including the kidney. Gut microbial dysbiosis contributes to SLE pathogenesis. An abnormal metabolism is a characteristic feature of SLE in which the inflammatory functions of CD4+ T cells rely on glycolysis. We have shown that treatment with 2-deoxy-D-glucose (2DG), a glycolysis inhibitor, reduced the expansion of germinal centers and eliminated the production of autoantibodies, ameliorating disease in lupus-prone mice, including (NZB × NZW)F1 and (NZW x BXSB)F1. Here we show that the 2DG treatment also maintained gut bacterial diversity, reduced the changes in bacterial populations that occurred as disease developed in these mice, and that it altered the distribution of fecal metabolites. We investigated the effect of fecal microbiota transplantation (FMT) from 2DG-treated or control mice into pre-autoimmune lupus-prone mice of the same strain. In both strains, FMT from 2DG-treated mice was highly protective, with a reduction or elimination of anti-dsDNA IgG production, immune cell activation, and renal pathology compared to FMT from control mice. Overall, our results demonstrated for the first time that the therapeutic effect of glucose inhibition in lupus is transferable through the gut microbiota. This implicates either a direct effect of glucose on pathogenic gut bacteria, or an indirect effect through the immune system normalized by glucose inhibition. Supported b R01 AI143313

Dysbiosis

Pathogenesis

10.4049/jimmunol.208.supp.174.02

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Enhanced expression of IL‐8 in normal human keratinocytes and human keratinocyte cell line HaCaT in vitro after stimulation with contact sensitizers., tolerogens and irritants

Experimental Dermatology (1994)

Mansour Mohamadzadeh Markus Miiller Thomas Hultsch Alexander Enk Joachim Saloga

Abstract To investigate the interleukin‐8 production of keratinocytes after stimulation in vitro we have used various agents: (i) contact sensi‐tizer (2,4‐dinitrofiuorobenzene, 3‐n‐penladecylcatechol); (ii) tolerogen (5‐methyl‐3‐n‐pentadecylcatechol); (iii) irritant (sodium lauryl sulfate). Interleukin‐8 gene expression was assessed by northern blot hybridization of the total cytoplasmic RNA extracted from subconfluent normal human keratinocyte cultures and the keratinocyte cell line HaCaT using a radiolabeled DNA probe specific for human interleukin‐8. Intcrleukin‐8 gene expression was markedly increased upon in vitro stimulation after 1‐6 h with contact sensitizers, tolerogen and the irritant. In contrast, in‐terlcukin‐8 production was not detectable in unstimulatcd normal human keratinocytes or the HaCaT keratinocyte cell line. These results suggest that the induction and production of interleukin‐8 is a response to nonspecific stimuli and may play a critical role in the early response to immuno‐genic or inflammatory signals in man.

HaCaT

Northern blot

Human skin

Interleukin 20

10.1111/j.1600-0625.1994.tb00292.x

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Citations (55)

Vitamin B12 coordinates ileal epithelial cell and microbiota functions to resist Salmonella infection in mice

The Journal of Experimental Medicine (2022)

Yong Ge Mojgan Zadeh Mansour Mohamadzadeh

Deprivation of vitamin B12 (VB12) is linked to various diseases, but the underlying mechanisms in disease progression are poorly understood. Using multiomic approaches, we elucidated the responses of ileal epithelial cells (iECs) and gut microbiome to VB12 dietary restriction. Here, VB12 deficiency impaired the transcriptional and metabolic programming of iECs and reduced epithelial mitochondrial respiration and carnitine shuttling during intestinal Salmonella Typhimurium (STm) infection. Fecal microbial and untargeted metabolomic profiling identified marked changes related to VB12 deficiency, including reductions of metabolites potentially activating mitochondrial β-oxidation in iECs and short-chain fatty acids (SCFAs). Depletion of SCFA-producing microbes by streptomycin treatment decreased the VB12-dependent STm protection. Moreover, compromised mitochondrial function of iECs correlated with declined cell capability to utilize oxygen, leading to uncontrolled oxygen-dependent STm expansion in VB12-deficient mice. Our findings uncovered previously unrecognized mechanisms through which VB12 coordinates ileal epithelial mitochondrial homeostasis and gut microbiota to regulate epithelial oxygenation, resulting in the control of aerobic STm infection.

Intestinal mucosa

10.1084/jem.20220057

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Citations (29)

Data from Locoregional Effects of Microbiota in a Preclinical Model of Colon Carcinogenesis

Sarah Tomkovich Ye Yang Kathryn Winglee Josée Gauthier Marcus Mühlbauer

<div>AbstractInflammation and microbiota are critical components of intestinal tumorigenesis. To dissect how the microbiota contributes to tumor distribution, we generated germ-free (GF) ApcMin/+and ApcMin/+;Il10−/− mice and exposed them to specific-pathogen-free (SPF) or colorectal cancer-associated bacteria. We found that colon tumorigenesis significantly correlated with inflammation in SPF-housed ApcMin/+;Il10−/−, but not in ApcMin/+mice. In contrast, small intestinal neoplasia development significantly correlated with age in both ApcMin/+;Il10−/− and ApcMin/+ mice. GF ApcMin/+;Il10−/− mice conventionalized by an SPF microbiota had significantly more colon tumors compared with GF mice. Gnotobiotic studies revealed that while Fusobacterium nucleatum clinical isolates with FadA and Fap2 adhesins failed to induce inflammation and tumorigenesis, pks+Escherichia coli promoted tumorigenesis in the ApcMin/+;Il10−/− model in a colibactin-dependent manner, suggesting colibactin is a driver of carcinogenesis. Our results suggest a distinct etiology of cancers in different locations of the gut, where colon cancer is primarily driven by inflammation and the microbiome, while age is a driving force for small intestine cancer. Cancer Res; 77(10); 2620–32. ©2017 AACR.</div>

10.1158/0008-5472.c.6508515

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Anthrax, toxins and vaccines: a 125-year journey targetingBacillus anthracis

Expert Review of Anti-infective Therapy (2009)

Jean‐Nicolas Tournier Robert G. Ulrich Anne Quesnel‐Hellmann Mansour Mohamadzadeh Bradley G. Stiles

Bacillus anthracis is the causative agent of anthrax, a disease that plagues both humans and various animal species. Effective vaccines are available, but those approved for human use are crude culture supernatants that require multiple injections and a yearly boost. Many experts agree that it is now time for the next generation of human vaccines against anthrax. Accordingly, this review will succinctly focus upon: pathogenesis of B. anthracis, with particular emphasis upon the immune system; the pertinent biophysical nature of protective antigen, which includes how the protein toxin component affords protection as a vaccine target; alternative methods for improving protective antigen as an immunogen; and additional B. anthracis antigens that might further sustain protective titers in humans. In addition to a better understanding of the disease process elicited by B. anthracis, which will logically lead to better vaccines (and therapeutics), there also needs to be the same level of open-mindedness applied to the politics of anthrax.

Bacillus anthracis

Anthrax vaccines

Immunogen

Anthrax toxin

10.1586/14787210.7.2.219

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Citations (55)

Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice

iScience (2023)

Ahmed S. Elshikha Yong Ge Josephine R. Brown Nathalie Kanda Mojgan Zadeh

Gut dysbiosis has been associated with lupus pathogenesis, and fecal microbiota transfers (FMT) from lupus-prone mice shown to induce autoimmune activation into healthy mice. The immune cells of lupus patients exhibit an increased glucose metabolism and treatments with 2-deoxy-D-glucose (2DG), a glycolysis inhibitor, are therapeutic in lupus-prone mice. Here, we showed in two models of lupus with different etiologies that 2DG altered the composition of the fecal microbiome and associated metabolites. In both models, FMT from 2DG-treated mice protected lupus-prone mice of the same strain from the development of glomerulonephritis, reduced autoantibody production as well as the activation of CD4+ T cells and myeloid cells as compared to FMT from control mice. Thus, we demonstrated that the protective effect of glucose inhibition in lupus is transferable through the gut microbiota, directly linking alterations in immunometabolism to gut dysbiosis in the hosts.

Dysbiosis

Pathogenesis

10.1016/j.isci.2023.107122

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Citations (7)

Supplementary Materials and Methods, Supplementary Figures 1 through 5, and Supplementary Tables 1 through 3 from Locoregional Effects of Microbiota in a Preclinical Model of Colon Carcinogenesis

Sarah Tomkovich Yang Ye Kathryn Winglee Josée Gauthier Marcus Mühlbauer

Supplementary Materials and Methods describing 16S rRNA sequencing analysis. Figure S1. PCR detection of F. nucleatum adhesins. Figure S2. ApcMin/+;Il10-/- mice have increased colon proliferation. Figure S3. Bacteria do not promote colon inflammation and tumorigenesis in ApcMin/+ mice. Figure S4. Microbiota promote proximal colon proliferation in ApcMin/+;Il10-/- mice. Figure S5. Colibactin promotes CRC development in AOM/Il10-/- mice. Table S1. Spearman correlations and corresponding p values from linear models used to generate Figure 3. Table S2. V1-V3 MiSeq Primers. Table S3. Accession numbers for 16S rRNA sequenced ApcMin/+;Il10-/- stool samples from Figure 3.

10.1158/0008-5472.22412775

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Novel oral targeted vaccines for cancer & pathogen challenges

Journal of Vaccines & Vaccination (2013)

Mansour Mohamadzadeh

Vaccine adjuvant

Immunopharmacology

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Human Keratinocyte-Derived IL-12 Affects LC-Induced Allogeneic T-Cell Responses