AUTHOR=Haake David A. , Matsunaga James TITLE=Leptospiral Immunoglobulin-Like Domain Proteins: Roles in Virulence and Immunity JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.579907 DOI=10.3389/fimmu.2020.579907 ISSN=1664-3224 ABSTRACT=

The virulence mechanisms required for infection and evasion of immunity by pathogenic Leptospira species remain poorly understood. A number of L. interrogans surface proteins have been discovered, lying at the interface between the pathogen and host. Among these proteins, the functional properties of the Lig (leptospiral immunoglobulin-like domain) proteins have been examined most thoroughly. LigA, LigB, and LigC contain a series of, 13, 12, and 12 closely related domains, respectively, each containing a bacterial immunoglobulin (Big) -like fold. The multidomain region forms a mostly elongated structure that exposes a large surface area. Leptospires wield the Lig proteins to promote interactions with a range of specific host proteins, including those that aid evasion of innate immune mechanisms. These diverse binding events mediate adhesion of L. interrogans to the extracellular matrix, inhibit hemostasis, and inactivate key complement proteins. These interactions may help L. interrogans overcome the physical, hematological, and immunological barriers that would otherwise prevent the spirochete from establishing a systemic infection. Despite significant differences in the affinities of the LigA and LigB proteins for host targets, their functions overlap during lethal infection of hamsters; virulence is lost only when both ligA and ligB transcription is knocked down simultaneously. Lig proteins have been shown to be promising vaccine antigens through evaluation of a variety of different adjuvant strategies. This review serves to summarize current knowledge of Lig protein roles in virulence and immunity and to identify directions needed to better understand the precise functions of the Lig proteins during infection.