Myeloid Differentiation Factor 88 and Interleukin-1R1 Signaling Contribute to Resistance to Coccidioides immitis
Coccidioidomycosis is a major cause of morbidity and mortality in regions of North America where the disease is endemic. Little is known about why the infection in a minority of apparently healthy people disseminates outside the lung, but this could be due to an aberrant innate immune response to the fungus. Using a mouse model of infection, Viriyakosol et al. (e00028-18) show that signaling through interleukin-1R1 (IL-1R1) is important for host defense. MyD88- and IL-R1-deficient mice are more susceptible to infection, and a susceptible strain of mice produces such a large amount of IL-1Ra (antagonist) in the lungs that IL-1 is effectively neutralized. IL-1Ra is secreted by dendritic cells stimulated with fungal spherules independent of MyD88 or Dectin-1. Studies of IL-1-regulatory cytokines in infected humans are needed.
The Adjuvant Bordetella Colonization Factor A (BcfA) Elicits Th1/17 Immunity and Attenuates Th2 Responses
Pertussis resurgence is attributed to suboptimal immune responses generated by current acellular pertussis vaccines (aPV). Jennings-Gee et al. (e00935-17) show that BcfA, an outer membrane protein, has adjuvant function and modifies the Th1/2-skewed responses generated by alum and aPV to a more protective Th1/17 phenotype. Inclusion of BcfA in aPV reduced bacterial numbers in the lung, elicited strong gamma interferon and interleukin-17 (IL-17) and a higher ratio of IgG2/IgG1 serum antibodies, and simultaneously attenuated production of the Th2 cytokine IL-5. The ability of BcfA to induce Th1/17 responses and attenuate Th2 responses is broadly applicable to improving immunity against other pathogens for which Th1/17 responses are critical for protection.
Pathogenic Spotted Fever Group Rickettsia Transits between Tick and Vertebrate Hosts
Previous studies demonstrated a central role for intracellular Rickettsia actin-based motility in cell-to-cell spread in mammalian cells and animal models. However, it was not known what role actin-based motility plays in rickettsial dissemination in arthropod hosts. Using Rickettsia parkeri mutants defective in actin-based motility, Harris et al. (e00123-18) demonstrate that rickettsial proteins surface cell antigen 2 (Sca2) and RickA drive phases of actin-based motility in a tick-derived cell line but that neither is required for dissemination in the tick vector Amblyomma maculatum. These data suggest that Rickettsia employs redundant or distinct mechanisms of dissemination in vertebrate and arthropod hosts and provide a working model for evaluating rickettsial protein function in actively feeding ticks.
- Copyright © 2018 American Society for Microbiology.
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- Myeloid Differentiation Factor 88 and Interleukin-1R1 Signaling Contribute to Resistance to Coccidioides immitis
- The Adjuvant Bordetella Colonization Factor A (BcfA) Elicits Th1/17 Immunity and Attenuates Th2 Responses
- Pathogenic Spotted Fever Group Rickettsia Transits between Tick and Vertebrate Hosts
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