Professional Education


  • Bachelor of Science, University of California Irvine (2006)
  • Master of Science, San Francisco State University (2008)
  • Doctor of Philosophy, University of California Irvine (2014)

Stanford Advisors


All Publications


  • Type II Toxoplasma gondii Induction of CD40 on Infected Macrophages Enhances Interleukin-12 Responses INFECTION AND IMMUNITY Morgado, P., Sudarshana, D. M., Gov, L., Harker, K. S., Lam, T., Casali, P., Boyle, J. P., Lodoen, M. B. 2014; 82 (10): 4047-4055

    Abstract

    Toxoplasma gondii is an obligate intracellular parasite that can cause severe neurological disease in infected humans. CD40 is a receptor on macrophages that plays a critical role in controlling T. gondii infection. We examined the regulation of CD40 on the surface of T. gondii-infected bone marrow-derived macrophages (BMdMs). T. gondii induced CD40 expression both at the transcript level and on the cell surface, and interestingly, the effect was parasite strain specific: CD40 levels were dramatically increased in type II T. gondii-infected BMdMs compared to type I- or type III-infected cells. Type II induction of CD40 was specific to cells harboring intracellular parasites and detectable as early as 6 h postinfection (hpi) at the transcript level. CD40 protein expression peaked at 18 hpi. Using forward genetics with progeny from a type II × type III cross, we found that CD40 induction mapped to a region of chromosome X that included the gene encoding the dense granule protein 15 (GRA15). Using type I parasites stably expressing the type II allele of GRA15 (GRA15II), we found that type I GRA15II parasites induced the expression of CD40 on infected cells in an NF-κB-dependent manner. In addition, stable expression of hemagglutinin-tagged GRA15II in THP-1 cells resulted in CD40 upregulation in the absence of infection. Since CD40 signaling contributes to interleukin-12 (IL-12) production, we examined IL-12 from infected macrophages and found that CD40L engagement of CD40 amplified the IL-12 response in type II-infected cells. These data indicate that GRA15II induction of CD40 promotes parasite immunity through the production of IL-12.

    View details for DOI 10.1128/IAI.01615-14

    View details for Web of Science ID 000341935100006

    View details for PubMedID 25024369

  • Complement Protein C1q Directs Macrophage Polarization and Limits Inflammasome Activity during the Uptake of Apoptotic Cells JOURNAL OF IMMUNOLOGY Benoit, M. E., Clarke, E. V., Morgado, P., Fraser, D. A., Tenner, A. J. 2012; 188 (11): 5682-5693

    Abstract

    Deficiency in C1q, the recognition component of the classical complement cascade and a pattern recognition receptor involved in apoptotic cell clearance, leads to lupus-like autoimmune diseases characterized by auto-antibodies to self proteins and aberrant innate immune cell activation likely due to impaired clearance of apoptotic cells. In this study, we developed an autologous system using primary human lymphocytes and human monocyte-derived macrophages (HMDMs) to characterize the effect of C1q on macrophage gene expression profiles during the uptake of apoptotic cells. C1q bound to autologous apoptotic lymphocytes modulated expression of genes associated with JAK/STAT signaling, chemotaxis, immunoregulation, and NLRP3 inflammasome activation in LPS-stimulated HMDMs. Specifically, C1q sequentially induced type I IFNs, IL-27, and IL-10 in LPS-stimulated HMDMs and IL-27 in HMDMs when incubated with apoptotic lymphocyte conditioned media. Coincubation with C1q tails prevented the induction of type I IFNs and IL-27 in a dose-dependent manner, and neutralization of type I IFNs partially prevented IL-27 induction by C1q. Finally, C1q decreased procaspase-1 cleavage and caspase-1-dependent cleavage of IL-1β suggesting a potent inhibitory effect of C1q on inflammasome activation. These results identify specific molecular pathways induced by C1q to suppress macrophage inflammation and provide potential therapeutic targets to control macrophage polarization and thus inflammation and autoimmunity.

    View details for DOI 10.4049/jimmunol.1103760

    View details for Web of Science ID 000304282200054

    View details for PubMedID 22523386

  • Toxoplasma gondii Induces B7-2 Expression through Activation of JNK Signal Transduction INFECTION AND IMMUNITY Morgado, P., Ong, Y., Boothroyd, J. C., Lodoen, M. B. 2011; 79 (11): 4401-4412

    Abstract

    Toxoplasma gondii is a globally distributed parasite pathogen that infects virtually all warm-blooded animals. A hallmark of immunity to acute infection is the production of gamma interferon (IFN-?) and interleukin-12 (IL-12), followed by a protective T cell response that is critical for parasite control. Naïve T cell activation requires both T-cell receptor (TCR) stimulation and the engagement of costimulatory receptors. Because of their important function in activating T cells, the expression of costimulatory ligands is believed to be under tight control. The molecular mechanisms governing their induction during microbial stimulation, however, are not well understood. We found that all three strains of T. gondii (types I, II, and III) upregulated the expression of B7-2, but not B7-1, on the surface of mouse bone marrow-derived macrophages. Additionally, intraperitoneal infection of mice with green fluorescent protein (GFP)-expressing parasites resulted in enhanced B7-2 levels specifically on infected, GFP(+) CD11b(+) cells. B7-2 induction occurred at the transcript level, required active parasite invasion, and was not dependent on MyD88 or TRIF. Functional assays demonstrated that T. gondii-infected macrophages stimulated naïve T cell proliferation in a B7-2-dependent manner. Genome-wide transcriptional analysis comparing infected and uninfected macrophages revealed the activation of mitogen-activated protein kinase (MAPK) signaling in infected cells. Using specific inhibitors against MAPKs, we determined that parasite-induced B7-2 is dependent on Jun N-terminal protein kinase (JNK) but not extracellular signal-regulated kinase (ERK) or p38 signaling. We also observed that T. gondii-induced B7-2 expression on human peripheral blood monocytes is dependent on JNK signaling, indicating that a common mechanism of B7-2 regulation by T. gondii may exist in both humans and mice.

    View details for DOI 10.1128/IAI.05562-11

    View details for Web of Science ID 000296352400012

    View details for PubMedID 21911468