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=<p>The virulence mechanisms required for infection and evasion of immunity by pathogenic <italic>Leptospira</italic> species remain poorly understood. A number of <italic>L. interrogans</italic> surface proteins have been discovered, lying at the interface between the pathogen and host. Among these proteins, the functional properties of the Lig (<underline>l</underline>eptospiral <underline>i</underline>mmuno<underline>g</underline>lobulin-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 <underline>b</underline>acterial <underline>i</underline>mmuno<underline>g</underline>lobulin (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 <italic>L. interrogans</italic> to the extracellular matrix, inhibit hemostasis, and inactivate key complement proteins. These interactions may help <italic>L. interrogans</italic> 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 <italic>ligA</italic> and <italic>ligB</italic> 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.</p>