Title

Regulation of the Host Immune System by the Hookworm Ancylostoma ceylanicum

Presenter Information

Nicholas Diliani

Document Type

Oral Presentation

Location

SURC 137B

Start Date

16-5-2013

End Date

16-5-2013

Abstract

Approximately one billion people are currently infected with hookworm. Past studies suggest that infection with these intestinal nematodes is associated with impaired cellular immunity. Despite its high prevalence and the concomitant immune suppression seen in infected individuals, little research has been done on host immunosuppression by hookworm. Our study focused on characterizing the mechanisms by which hookworm suppresses the host immune response. We hypothesized that hookworm secretes proteins to shift the immune system away from a normal, healing TH2 response, to a non-healing mixed TH1/TH2 immune response. Splenocytes and draining lymph node cells from mice injected with excretory/secretory (ES) proteins showed decreased proliferation in response to a mitogen while also having increased nitric oxide secretion. Analysis by fluorescence-activated cell sorting revealed that mice injected with ES had reduced percentages of CD4+ T cells while CD8+ T cell numbers were unaffected indicating shift in immune response from TH2 to a mixed TH1/TH2. Analysis of antibody and cytokine levels revealed that injection with ES proteins decreased Immunoglobulin-G antibody production while also decreasing IL-4 and increasing IFN-γ cytokine production suggesting decreased B cell activation and a shift towards a TH1 immune response. Together, these data demonstrate that immunosuppression by hookworm infection is caused by ES proteins and detail the mechanism behind the shift in immune response in infected hosts. Work is underway to identify the hookworm individual proteins involved in the suppression of the vertebrate host.

Faculty Mentor(s)

Blaise Dondji

Additional Mentoring Department

Biological Sciences

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May 16th, 12:20 PM May 16th, 12:40 PM

Regulation of the Host Immune System by the Hookworm Ancylostoma ceylanicum

SURC 137B

Approximately one billion people are currently infected with hookworm. Past studies suggest that infection with these intestinal nematodes is associated with impaired cellular immunity. Despite its high prevalence and the concomitant immune suppression seen in infected individuals, little research has been done on host immunosuppression by hookworm. Our study focused on characterizing the mechanisms by which hookworm suppresses the host immune response. We hypothesized that hookworm secretes proteins to shift the immune system away from a normal, healing TH2 response, to a non-healing mixed TH1/TH2 immune response. Splenocytes and draining lymph node cells from mice injected with excretory/secretory (ES) proteins showed decreased proliferation in response to a mitogen while also having increased nitric oxide secretion. Analysis by fluorescence-activated cell sorting revealed that mice injected with ES had reduced percentages of CD4+ T cells while CD8+ T cell numbers were unaffected indicating shift in immune response from TH2 to a mixed TH1/TH2. Analysis of antibody and cytokine levels revealed that injection with ES proteins decreased Immunoglobulin-G antibody production while also decreasing IL-4 and increasing IFN-γ cytokine production suggesting decreased B cell activation and a shift towards a TH1 immune response. Together, these data demonstrate that immunosuppression by hookworm infection is caused by ES proteins and detail the mechanism behind the shift in immune response in infected hosts. Work is underway to identify the hookworm individual proteins involved in the suppression of the vertebrate host.