**3. Pathogenesis**

Leptospirosis is termed as "storm of abortion" and is farm economy jeopardizing malaise [42]. *Leptospira* spread in direct and indirect ways, while the latter is a more pronounced method of transfer. Direct transmission involves through infected urine, post abortion uterine discharge, sexual contact, and infected placentae. Indirect involves contact with environment. Bacteria get entry to skin through abraded skin that follows hematogenous spread in the body. Bacteria result vasculitis that in turn results into either direct cytotoxic injury and immunological reactions or massive migration of fluid from intravascular to interstitial compartment. The latter results in renal dysfunction and vascular injury to internal organs. Pathogenic *Leptospira* could not be phagocytosed by macrophages and neutrophils, but if there are specific antibodies present, it can be phagocytosed [22]. It has been suggested that the animals are susceptible to severe or acute leptospirosis caused by increase in production of anti-inflammatory cytokines and chemokines [23]. Although pathogenic *Leptospira* are complementary to bactericidal activity, it has long been known that *Leptospira* has antimicrobial activity [43]. In most studies, leptospiral proteins that bind to one or more components are usually identified in recombinant form. Adhesin LenA (LfhA, Lsa 24) and Len B also bind to complementary regulatory protein factor H [44, 45]. Complement resistance to pathogenic *Leptospira* can also bind to the complement module C4BP, which catalyzes the cleavage of C4b [24]. It leads to decrease in surface deposition of subsequent components of the complement, where decaying species are not available. In subsequent studies, this activity was attributed to the new leptospiral proteins LcpA and Lsa30 [46]. Interestingly, ligand proteins that interact with many host ECM hosts and other proteins also interact with the complement regulators H, FHL-1, FHR1, and C4BP [25]. Surprisingly, the *Leptospira* elongation factor Tu shows a superficial effect and interaction with factor H, as well as binding to many purified host proteins, which leads to its diversity, the so-called "moonlighting protein" [25]. Most of the above studies provide indirect evidence of the role of *Leptospira* protein in the prevention of complement, but recently, it has been shown that the pathogenicity and non-urogenital fecundity of the three complement pathways, including factor B [26]. C2 and C4b are identified in the culture supernatant of the *Leptospira* cleavage component. In fact, inactivation of the above two proteins, Lig B and Len B, does not have a significant effect on pathogenicity [27, 28, 47]. Similarly, functional redundancy must also be considered: LenA and LenB. All proteins have structural and functional similarities to the endostatin of mammals [44].
