Interaction of Leptospira with the Innate Immune System

Abstract

Innate immunity encompasses immediate host responses that detect and respond to microbes. Besides recognition by the complement system (see the chapter by A. Barbosa, this volume), innate immunity concerns cellular responses. These are triggered through recognition of conserved microbial components (called MAMPs) by pattern recognition receptors (PRRs), leading, through secretion of cytokines, antimicrobial peptides, and immune mediators, to cellular recruitment and phagocytosis. Leptospira spp. are successful zoonotic pathogenic bacteria that obviously overcome the immune system of their hosts. The first part of this chapter summarizes what is known about leptospires recognition and interaction with phagocytes and other innate immune cells, and the second part describes specific interactions of leptospiral MAMPs with PRRs from the TLR and NLR families. On the one hand, pathogenic leptospires appear to escape macrophage and neutrophil phagocytosis. On the other hand, studies about PRR sensing of leptospires remain very limited, but suggest that pathogenic leptospires escape some of the PRRs in a host-specific manner, due to peculiar cell wall specificities or post-translational modifications that may impair their recognition. Further studies are necessary to clarify the mechanisms and consequences of leptospiral escape on phagocytic functions and hopefully give clues to potential therapeutic strategies aimed at restoring the defective activation of PRRs by pathogenic Leptospira spp.

Recent findings related to immune responses against leptospirosis and novel strategies to prevent infection

“…Linked to complement evasion, pathogenic leptospires largely escape phagocytosis unless opsonized by specific antibodies [22]. Neutrophils are barely efficient to counteract pathogenic leptospires, but it has been shown ex vivo that L. interrogans are killed by Neutrophil Extracellular Traps (NET) [23].…”

“…Consistent with this result, whilst WT mice are largely asymptomatic, TLR4 deficient mice are highly sensitive to leptospirosis, and may die after intraperitoneal infection with virulent L. interrogans. In human, murine, bovine and pig cells, leptospiral LPS is also recognized by TLR2, which is the lipoprotein receptor [22,31,32]. Since leptospiral lipid A is not recognized by TLR2, the TLR2 recognition is most probably due to a non-identified lipopeptide tightly attached to the core or Oantigen part of the LPS.…”

Leptospiraspecies promote a pro‐inflammatory phenotype in human neutrophils

“…Together, the findings in human and murine studies suggest that neutrophils do not seem to be an efficient defence factor for pathogenic Leptospira (Werts, 2017). On the other hand, it is well known that human leptospirosis presents neutrophilia, which correlates with severity (de Silva et al, 2018;Lindow et al, 2016;Raffray et al, 2016) and the pathogenic serovar involved (Craig et al, 2013).…”

Murine Models for Leptospirosis Kidney Disease

“…However, some immune-compromised mice, and mice deficient in some innate immune receptors, have proved sensitive to acute leptospirosis and helped to understand the important factors driving protection or disease ( Fig. 1 , 2 , and for a comprehensive review and historical perspective, see [8,19] ).…”

“…MyD88 and TRIF activation lead to NF-κB and MAP kinases activation, but in addition, TRIF stimulation leads to the activation of the IRF3 transcription factor. Altogether, these signaling pathways contribute to potent proinflammatory, antimicrobial, and type I interferon responses, aimed at alerting and recruiting phagocytes and fighting microbes [19] .…”